- Synthesis, characterization and computational studies of 4-[(Pyridine-3-carbonyl)-hydrazonomethyl]-benzoic acid
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A new hydrazone derivative compound, 4-[(Pyridine-3-carbonyl)-hydrazonomethyl]-benzoic acid, C15H11N3O, was obtained and characterized by 1H NMR, 13C NMR and UV–Vis, FT-IR and FT-Raman spectroscopy techniques. Molecular geometry, vibrational wavenumbers, frontier molecular orbital and non-linear optical (NLO) property of the title compound were calculated using ab initio Hartree-Fock (HF) and Density Functional Theory (DFT), employing B3LYP functional at 6–311++G (d,p) basis set. 1H and 13C NMR chemical shifts were calculated by using the gauge in dependent atomic orbital (GIAO) method at the HF and B3LYP methods with different basis sets. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were obtained from DFT LSDA methods with 6–311++G (d,p) basis set. The NLO behaviour of the title compound has been studied by determining the electric dipole moment (μ) and hyperpolarizability (β) using both B3LYP/6–311++G (d,p) and HF/6–311++G (d,p) methods. The energy gaps s(ΔEgap=ELUMO?EHOMO) of title molecule were calculated at 4.15, 2.77 and 9.81 eV with DFT-B3LYP/6–311++ G (d,p), DFT-LSDA/6–311++ G (d,p) and HF/6–311++ G (d,p) level of theory, respectively. The calculated experimentally energy gap was found as 2.827 eV.
- Elif ?ztürkkan ?zbek, Füreya,Kalay, Erbay,Necefo?lu, Hacali,U?urlu, Güventürk
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- A novel coumarin-based fluorescence chemosensor for Al3+ and its application in cell imaging
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As an efficient turn-on fluorescent chemosensor for Al3+, a new coumarin derivative (CND) has been designed and synthesized by the condensation of 8-formyl-7-hydroxycoumarin with niacin hydrazide. The spectroscopic studies revealed that the sensor CND exhibited a remarkable fluorescence enhancement towards Al3+ with high selectivity and sensitivity in EtOH-HEPES (95:5, v/v, pH = 7.40), which was attributed to the photoinduced electron transfer (PET) and –C[dbnd]N isomerization mechanism. Fluorescence titration calculations data showed that the detection limit and the association constants of CND for Al3+ were found to be 2.51 × 10?7 M and 9.64 × 104 M?1, respectively. The results of experiments, including Job's plot, 1H NMR titration and ESI-MS, revealed that the stoichiometric binding between CND and Al3+ was 1:1. The investigations of the pH dependency of CND for Al3+ detection, and the cell imaging suggested the sensor CND could be promisingly applied for the recognition of Al3+ in biological cells.
- Zhu, Guohua,Huang, Yang,Wang, Chun,Lu, Linxia,Sun, Tongming,Wang, Miao,Tang, Yanfeng,Shan, Doudou,Wen, Shuijin,Zhu, Jinli
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- Theoretical and experimental assesment of structural, spectroscopic, electronic and nonlinear optical properties of two aroylhydrazone derivative
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Two aroylhydrazone, N'-(pyridine-4-ylmethylene)nicotic acid hydrazide (1) and N'-(pyridine-3-ylmethylene)nicotic acid hydrazide (2), were synthesized and their structures were determined by single-crystal X-ray diffraction analysis. The X-ray analysis indicated that the compound 1 was crystallized in triclinic crystal system with P -1space group a = 8.7899 (2) ?, b = 10.8983 (3) ?, c = 11.7726 (3) ?, α= 89.952 (3)°, β = 88.684 (3)°, γ= 75.293 (2)°, V = 1090.50 (5) ?3 and Z = 4 and compound 2 was crystallized in monoclinic crystal system with P21/c space group, a = 11.9239 (3) ?, b = 8.6495 (2) ?, c = 11.1021 (3) ?, α= 90 (3)°, β = 111.664 (3) (3)°, γ= 90°, V = 1064.14 (5) ?3 and Z = 4. Intermolecular interactions of the compounds were determined by Hirhfeld Surface Analysis. The H ··· H interactions with 37.9percent (for compound 1) and 37.5percent (for compound 2) contributions are the most important interactions to the overall crystal packings. FT-IR, Raman, 1H and 13C NMR and UV–Vis spectroscopy methods were used for spectroscopic characterization of the compounds. The spectroscopic properties of the compounds were calculated theoretically by using Density Functional Theory (DFT) with B3LYP and ab initio Hartree-Fock (HF) methods at different basis sets. A correlation was found between the theoretical and experimental values for the spectroscopic results. Moreover, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), electric dipole moment (μ), polarizability (α) and hyperpolarizability (β) of the compounds were computed both DFT/B3LYP/6–311++G(d,p) and ab initio HF/6–311++G(d,p) methods. The calculated first hyperpolarizability value at the DFT/B3LYP/6–31++G (d,p) level of compound 1 with dimer structure is 18.14 times larger than urea, the standard nonlinear optical material. So, this value implies that compound 1 considered have potential candidates for designing high quality nonlinear optical materials. The energy gap (ΔEgap) and Molecular Electrostatic Potential (MEP) of the compounds were investigated. The structural and vibration frequency values calculated theoretically were compared with the experimental values.
- ?ztürkkan ?zbek, Füreya Elif,H?kelek, Tuncer,Kalay, Erbay,Necefo?lu, Hacali,U?urlu, Güventürk
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- New heterocyclic Schiff base-metal complex: Synthesis, characterization, density functional theory study, and antimicrobial evaluation
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A new series of heterocyclic Schiff base complexes derived from the condensation of nicotinohydrazide with different heterocyclic aldehyde, followed by metalation with Co (II) and Cu (II) metal ions. The chemical structures of the synthesized compounds have been characterized by elemental analysis, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, ultraviolet–visible spectroscopy, and magnetic susceptibility. The spectral and magnetic data confirmed their chemical structures, furthermore, the geometry of Cu (II) and Co (II) complexes were square-planar or distorted tetrahedral. X-ray diffraction measurements supported the crystalline structures of the metal complexes rather than the amorphous form of the parent Schiff bases. Thermogravimetric analysis revealed the upgrading of the thermal stability of metal complexes compared to their Schiff base ligands. Antimicrobial efficacies of the Schiff base ligands and their corresponded metal complexes were screened against Staphylococcus aureus and Bacillus subtilis as Gram-positive bacteria, Escherichia coli, and Proteus vulgaris as Gram-negative bacteria, and fungi Aspergillus flavus, Candida albicans. The antimicrobial inhibitory data revealed higher antimicrobial activities of metal complexes compared to their Schiff base ligands. Density functional theory module by Gaussian 09 W software proved the chemical reactivity of the prepared Schiff base ligands based on the total energy, energy gap, EHOMO, and ELUMO energies.
- Hashem, Heba E.,Mohamed, Eslam A.,Farag, Ahmed A.,Negm, Nabel A.,Azmy, Eman A. M.
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- Synthesis, structural, spectroscopic, and thermal studies of some transition-metal complexes of a ligand containing the amino mercapto triazole moiety
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A new series of transition-metal complexes of Schiff base ligand containing the amino mercapto triazole moiety (HL) was prepared. The Schiff base and its metal complexes were elucidated by different spectroscopic techniques (infrared [IR], 1H nuclear magnetic resonance, UV–Visible, mass, and electron spin resonance [ESR]), and magnetic moment and thermal studies. Quantum chemical calculations have been carried out to study the structure of the ligand and some of its complexes. The IR spectra showed that the ligand is chelated with the metal ion in a neutral, tridentate, and bidentate manner using NOS and NO donors in complexes 1–6, 10–12, and 7 and 8, respectively, whereas it behaves in a monobasic tridentate fashion using NOS donor sites in copper(II) nitrate complex (9). The magnetic moment and electronic spectra data revealed octahedral and square pyramidal geometries for complexes 2, 11, 12, and 5–8 and 10, respectively. However, the other complexes were found to have tetrahedral (4), trigonal bipyramidal (1 and 3), and square planar (9) structures. Thermal studies revealed that the chelates with different crystallized solvents undergo different types of interactions and the decomposition pathway ended with the formation of metal oxygen (MO) and metal sulfur (MS) as final products. The ESR spectrum of copper(II) complex 10 is axial in nature with hyperfine splitting with 2B1g as a ground state. By contrast, complexes 7 and 8 undergo distortion around the Cu(II) center, affording rhombic ESR spectra. The HL ligand and some of its complexes were screened against two bacterial species. Data showed that complex 12 demonstrated a better antibacterial activity than HL ligand and other chelates.
- El-Nahas, Ahmed M.,Emam, Sanaa M.,Tolan, Dina A.
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- Design, docking, synthesis, and characterization of novel N'(2-phenoxyacetyl) nicotinohydrazide and N'(2-phenoxyacetyl)isonicotinohydrazide derivatives as anti-inflammatory and analgesic agents
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Inflammation is the complex biological response of vascular tissues, which is partly determined by prostaglandins (PLA2). The cyclooxygenase (COX) enzyme exists in two isoforms: COX-1 and COX-2 and by the action of this, the PGs are produced. Besides, nonsteroidal anti-inflammatory drugs (NSAIDs) are therapeutic agents useful in the treatment of inflammation. Encouraged by this, the new derivatives of N'(2-phenoxyacetyl)nicotinohydrazide 9(a-e) and N'(2-phenoxyacetyl)isonicotinohydrazide 10(a-e) were designed, synthesized, characterized, and identified as remarkable anti-inflammatory and analgesic agents. These compounds were prepared in a series of steps starting with different phenol derivatives. Among the series, compound (10e) showed the highest IC50 value for COX-1 inhibition, whereas compounds (9e) and (10e) exhibited the highest COX-2SI. Further, molecular Docking Studies have been performed for the potent compound to check the three-dimensional geometrical view of the ligand binding to the targeted enzymes.
- Al-Ostoot, Fares Hezam,Khanum, Shaukath Ara,M, Pallavi H,Vivek, Hamse Kameshwar
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- Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
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Paragraph 0055-0056; 0070; 0090; 0093; 0095; 0102
(2021/07/24)
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- Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
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A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
- Liu, Jie,Zhang, Guang-Yu,Zhang, Zhe,Li, Bo,Chai, Fei,Wang, Qi,Zhou, Zi-Dan,Xu, Ling-Ling,Wang, Shou-Kai,Jin, Zhen,Tang, You-Zhi
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- Design and synthesis of novel furan, furo[2,3-d]pyrimidine and furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives as potential VEGFR-2 inhibitors
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Novel furan 6a-c, furo[2,3-d]pyrimidine 7a-f, 9, 10a-f, 12a,b, 14a-d and furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine 8a-f derivatives were designed based on their structural similarity to a previously described oxazole VEGFR-2 back pocket binding fragment. The designed compounds were synthesized and screened for their in vitro VEGFR-2 inhibitory activity where they exhibited good to moderate nanomolar inhibition with improved ligand efficiencies. 8b and 10c (IC50 = 38.72 ± 1.7 and 41.40 ± 1.8 nM, respectively) were equipotent to sorafenib and 6a, 6c, 7f, 8a, 8c, 10b, 10f, 12b, 14c and 14d showed good activity (IC50 = 43.31–98.31 nM). The furotriazolopyrimidines 8a-c and furopyrimidine derivative 10c were further evaluated for their in vitro antiproliferative activity against human umbilical vein endothelial cells (HUVECs) where 8b showed higher potency than sorafenib and resulted in cell cycle arrest at G2/M phase whereas 8c revealed good antiproliferative activity with cell cycle arrest at G1 phase. Moreover, 8a-c and 10c showed significant inhibitory effects on the invasion and migration of HUVECs. Molecular docking study was conducted to gain insight about the potential binding mode. The furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 8b and 8c represent interesting starting point for antiangiogenic compounds based on their activity and favorable drug likeness profiles.
- Abd El-Mageed, Menna M.A.,Eissa, Amal A.M.,Farag, Awatef El-Said,Osman, Essam Eldin A.
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- Development of Novel (+)-Nootkatone Thioethers Containing 1,3,4-Oxadiazole/Thiadiazole Moieties as Insecticide Candidates against Three Species of Insect Pests
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To improve the insecticidal activity of (+)-nootkatone, a series of 42 (+)-nootkatone thioethers containing 1,3,4-oxadiazole/thiadiazole moieties were prepared to evaluate their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal evaluation revealed that most of the title derivatives exhibited more potent insecticidal activities than the precursor (+)-nootkatone after the introduction of 1,3,4-oxadiazole/thiadiazole on (+)-nootkatone. Among all of the (+)-nootkatone derivatives, compound 8c (1 mg/mL) exhibited the best growth inhibitory (GI) activity against M. separata with a final corrected mortality rate (CMR) of 71.4%, which was 1.54- and 1.43-fold that of (+)-nootkatone and toosendanin, respectively; 8c also displayed the most potent aphicidal activity against M. persicae with an LD50 value of 0.030 μg/larvae, which was closer to that of the commercial insecticidal etoxazole (0.026 μg/larvae); and 8s showed the best larvicidal activity against P. xylostella with an LC50 value of 0.27 mg/mL, which was 3.37-fold that of toosendanin and slightly higher than that of etoxazole (0.28 mg/mL). Furthermore, the control efficacy of 8s against P. xylostella in the pot experiments under greenhouse conditions was better than that of etoxazole. Structure-activity relationships (SARs) revealed that in most cases, the introduction of 1,3,4-oxadiazole/thiadiazole containing halophenyl groups at the C-13 position of (+)-nootkatone could obtain more active derivatives against M. separata, M. persicae, and P. xylostella than those containing other groups. In addition, toxicity assays indicated that these (+)-nootkatone derivatives had good selectivity to insects over nontarget organisms (normal mammalian NRK-52E cells and C. idella and N. denticulata fries) with relatively low toxicity. Therefore, the above results indicate that these (+)-nootkatone derivatives could be further explored as new lead compounds for the development of potential eco-friendly pesticides.
- Cheng, Wanqing,Fan, Jiangping,Guo, Yong,Han, Meiyue,Ma, Nannan,Yan, Xiaoting,Yang, Ruige
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p. 15544 - 15553
(2022/01/03)
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- Discovery, synthesis and in combo studies of Schiff’s bases as promising dipeptidyl peptidase-IV inhibitors
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Abstract: Diabetes mellitus is a main global health apprehension. Macrovascular illnesses, neuropathy, retinopathy, and nephropathy are considered some of its severe hitches. Gliptins are a group of hypoglycemic agents that inhibit dipeptidyl peptidase-IV (DPP-IV) enzyme and support blood glucose-lowering effect of incretins. In the current research, synthesis, characterization, docking, and biological evaluation of fourteen Schiff’s bases 5a–f and 9a–h were carried out. Compound 9f revealed the best in vitro anti-DPP-IV activity of 35.7% inhibition at a concentration of 100?μM. Compounds 9c and 9f with the highest in vitro DPP-IV inhibition were subjected to the in vivo glucose-lowering test using vildagliptin as a positive inhibitor. Vildagliptin, 9c, and 9f showed significant reduction in the blood glucose levels of the treated mice after 30?min of glucose administration. Moreover, induced fit docking showed that these derivatives accommodated the enzyme binding site with comparable docking scores. Schiff’s bases can serve as promising lead for the development of new DPP-IV inhibitors. Graphical Abstract: [Figure not available: see fulltext.].
- Abu Khalaf, Reema,Al-Essa, Luay,Al-Shalabi, Eveen,Awad, Maha,Mefleh, Sara,Sabbah, Dima,Shabeeb, Ihsan
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- Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing–bacteria
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Joining the global fight against Tuberculosis, the world's most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a–m and 9a–c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 μg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 μg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49–7.81 μg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site.
- Elsayed, Zainab M.,Eldehna, Wagdy M.,Abdel-Aziz, Marwa M.,El Hassab, Mahmoud A.,Elkaeed, Eslam B.,Al-Warhi, Tarfah,Abdel-Aziz, Hatem A.,Abou-Seri, Sahar M.,Mohammed, Eman R.
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p. 384 - 393
(2021/01/13)
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- Carbazole-based semicarbazones and hydrazones as multifunctional anti-Alzheimer agents
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With the aim to combat a multi-faceted neurodegenerative Alzheimer’s disease (AD), a series of carbazole-based semicarbazide and hydrazide derivatives were designed, synthesized and assessed for their cholinesterase (ChE) inhibitory, antioxidant and biometal chelating activity. Among them, (E)-2-((9-ethyl-9H-carbazol-3-yl)methylene)-N-(pyridin-2-yl)hydrazinecarbothioamide (62) and (E)-2-((9-ethyl-9H-carbazol-3-yl)methylene)-N-(5-chloropyridin-2-yl)hydrazinecarbothioamide (63) emerged as the premier candidates with good ChE inhibitory activities (IC50 values of 1.37 μM and 1.18 μM for hAChE, IC50 values of 2.69 μM and 3.31 μM for EqBuChE, respectively). All the test compounds displayed excellent antioxidant activity (reduction percentage of DPPH values for compounds (62) and (63) were 85.67% and 84.49%, respectively at 100 μM concentration). Compounds (62) and (63) conferred specific copper ion chelating property in metal chelation study. Molecular docking studies of compounds (62) and (63) indicate strong interactions within the active sites of both the ChE enzymes. Besides that, these compounds also exhibited significant in silico drug-like pharmacokinetic properties. Thus, taken together, they can serve as a starting point in the designing of multifunctional ligands in pursuit of potential anti-AD agents that might further prevent the progression of ADs. Communicated by Ramaswamy H. Sarma.
- Chaudhary, Bharat N.,Gandhi, Bhumi,Kanhed, Ashish M.,Patel, Dushyant V.,Patel, Kirti V.,Patel, Kishan B.,Patel, Nirav R.,Prajapati, Navnit K.,Shah, Bhavik S.,Teli, Divya M.,Yadav, Mange Ram
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- Synthesis and structural study of some N-acyl-4-allylsemicarbazides and the product of their cyclization with a potential antimicrobial activity
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In this paper semicarbazide (2a-2h) and 1,2,4-trazole (3a-3h) derivatives with allyl group were synthesized. All compounds were tested in vitro for their antimicrobial activity showing different activity to E. coli, S. aureus, S. epidermidis, M. smegmatis, M. phlei and M. tuberculosis H37Ra. The antimicrobial activity is showed 2g against S. epidermidis, 3g against E. coli and S. epidermidis and 3h against E. coli. The crystal structure of determinations of 2b, 2d, 3b, 3c and 3e were undertaken in order to confirm the synthesis pathway and identification of their tautomeric forms in the crystalline state. Theoretical calculations showed that the physico-chemicals (logP) and electronic properties (MEP distribution, energy localization of HOMO and LUMO orbitals) are related to observed antimicrobial activity of investigated compounds. The molecular docking study carried out for the most active against M. tuberculosis compound 3b using the M. tuberculosis cytochrome P450 CYP121 showed that this compound binds to the active site of P450 by hydrogen bonds via water molecule with the amino acid residue of Met86A and molecule of hem.
- Drozd, Monika,Ginalska, Grazyna,Karczmarzyk, Zbigniew,Kowalczuk, Dorota,Morawiak, Maja,Pitucha, Monika,Swatko-Ossor, Marta,Urbanczyk-Lipkowska, Zofia,Wysocki, Waldemar
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- Efficient Synthesis of 1,4-Bis(5-aryl-1,3,4-oxadiazol-2-yl)-2,3,5,6-tetrafluorobenzenes
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Abstract: An efficient acid-catalyzed condensation between substituted benzohydrazides and 2,3,5,6-tetrafluoroterephthalic acid to form 1,4-bis(5-aryl-1,3,4-oxadiazol-2-yl)-2,3,5,6-tetrafluorobenzenes is reported. The products were isolated in 74–87% yield and were characterized by 1H NMR, IR, and mass spectra.
- Dhotre, B. K.,Khandebharad, A. U.,Pathan, A.,Raut, S. V.
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p. 1324 - 1326
(2020/10/02)
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- Synthesis of N'-nicotinoyl sulfonohydrazides and their antimicrobial activity
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N'-Nicotinoyl sulfonohydrazide derivatives 3-13 were synthesized from nicotinyl hydrazide and evaluated for their antimicrobial potential against Gram positive bacterial strains (Bacillus cereus, Bacillus subtilis, Corynebacterium diphtheriae, Staphylococcus fecalis, Staphylococcus aureus, and MRSA (Methicillin-resistant Staphylococcus aureus)) and Gram negative bacterial strains (Escherichia.coli, Pseudomonas aeruginosa, Salmonella ParatyphiB, Salmonella tyhpi). Compound 13 showed outstanding antibacterial activity against Staphylococcus fecalis and compounds 7 and 13 were found to be moderately activite against Salmonella Paratyphi B, shown by their zone of inhibition values. In addition to that compond 9 also showed moderate activity against Escherichia coli. All derivatives 3-13 were also subjected for the evaluation of their antifungal activity against Saccharomyces cerevisiae, Microsporum canin, Rhizopus, Aspergillus niger, Candida albicans, and Candida tropicalis. Compound 13 showed promising antifungal activity against Rhizopus sp. and compounds 9 and 10 showed moderate antifungal potential against Microsporum canis, Aspergillus niger, and Candida tropicalis. Other molecules demonstrated weak zone of inhibitions.
- Arshad, Zarina,Saied, Sumayya,Ali, Basharat,Salar, Uzma,Tauseef, Saima,Arshia,Ajaz, Munazza,Khan, Uroosa,Haider, Syed Moazzam,Taha, Muhammad,Khan, Khalid Mohammed
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p. 597 - 604
(2021/02/26)
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- Tetraphenyl ethylene Schiff base Al fluorescent probe and preparation method and application thereof
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The invention belongs to the field of fluorescent molecular probes, and discloses a tetraphenyl ethylene Schiff base Al fluorescent probe and a preparation method and application thereof. The preparation method comprises the following steps: dissolving 4-hydroxytetraphenyl ethylene and hexamethylenetetramine in a mixed solvent of acetic acid and trifluoroacetic acid for a reaction to obtain afirst intermediate product 4-hydroxy-5-aldehyde tetraphenyl ethylene, dissolving nicotinic acid in a methanol solvent, dropwise adding acetyl chloride into the solution, carrying out a reaction process to obtain a second intermediate product methyl nicotinate, dissolving the second intermediate product in a methanol solvent, adding hydrazine hydrate into the solution, carrying out a reaction process to obtain a third intermediate product nicotinamide, dissolving the first intermediate product and the third intermediate product in an ethanol solvent, and carrying out a reaction process to obtain the tetraphenyl ethylene Schiff base Al fluorescent probe. The fluorescent probe has specific selectivity on Al, and can be used for identifying Al in vitro, the fluorescence signal is basically not changed when acting with other common ions, the sensitivity is high, and the detection limit is low.
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Paragraph 0049; 0067; 0071
(2020/05/02)
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- Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors
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Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
- Alves, Marina A.,Chaves, Lorrane S.,Fernandes, Patrícia D.,Fraga, Carlos A. M.,Guerra, Fabiana S.,Rodrigues, Daniel A.,Sagrillo, Fernanda S.,Sant'Anna, Carlos M. R.,Thota, Sreekanth,de Sena M. Pinheiro, Pedro
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supporting information
(2020/02/25)
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- Synthesis and trypanocidal activity of novel pyridinyl-1,3,4-thiadiazole derivatives
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Herein, we present the design, synthesis and trypanocidal evaluation of sixteen new 1,3,4-thiadiazole derivatives from N-aminobenzyl or N-arylhydrazone series. All derivatives were assayed against the trypomastigote form of Trypanosoma cruzi, showing IC50 values ranging from 3 to 226 μM, and a better trypanocidal profile was demonstrated for the 1,3,4-thiadiazole-N-arylhydrazones (3a-g). In this series, the 2-pyridinyl fragment bound to the imine subunit of the hydrazine moiety presented pharmacophoric behavior for trypanocidal activity. Compounds 2a, 11a and 3e presented remarkable activity and excellent selectivity indexes. Compound 2a was also active against the intracellular amastigote form of T. cruzi. Moreover, its corresponding hydrochloride, compound 11a, showed the most promising profile, producing phenotypic changes similar to those caused by posaconazole, a well-known inhibitor of sterol biosynthesis. Thus, 1,3,4-thiadiazole derivative 11a could be considered a good prototype for the development of new drug candidates for Chagas disease therapy.
- Barbosa, Juliana M. C.,Bernardino, Patrícia,Decoté-Ricardo, Débora,Fraga, Carlos A. M.,Freitas, Rosana H. C. N.,Melo, Tatiana G.,Salom?o, Kelly,Sueth-Santiago, Vitor,Wardell, James L.,Wardell, Solange M. S. V.,da Silva, Edson F.
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- Structure based discovery of novel hexokinase 2 inhibitors
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Hexokinase 2 (HK2) is over-expressed in most of human cancers and has been proved to be a promising target for cancer therapy. In this study, based on the structure of HK2, we screened over 6 millions of compounds to obtain the lead. A total of 26 (E)-N′-(2,3,4-trihydroxybenzylidene) arylhydrazide derivatives were then designed, synthesized, and evaluated for their HK2 enzyme activity and IC50 values against two cancer cell lines. Most of the 26 target compounds showed excellently in vitro activity. Among them, compound 3j showed the strongest inhibitory effects on HK2 enzyme activity with an IC50 of 0.53 ± 0.13 μM and exhibited the most potent growth inhibition against SW480 cells with an IC50 of 7.13 ± 1.12 μM, which deserves further studies.
- Chen, Lixia,Gao, Suyu,Li, Hua,Li, Mingxue,Li, Xingzhou,Liu, Yang,Wu, Canrong,Yang, Kaiyin,Zhang, Yujie,Zheng, Mengzhu
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supporting information
(2020/02/04)
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- Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents
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Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7). Compounds 33h, 33i, 42f and 42h showed strong potencies against all tested cell lines with IC50 values ranging from 14.63 to 49.90 μM comparable to that of thalidomide (IC50 values ranging from 32.12 to 76.91 μM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 33h and 42f showed a significant reduction in TNF-α. Furthermore, compounds 33i and 42f exhibited significant elevation in CASP8 levels. Compounds 33i and 42f inhibited VEGF. In addition, compound 42f showed significant decrease in levels of NF-κB p65. Moreover, apoptosis and cell cycle tests of the most active compound 42f, were performed. The results indicated that compound 42f significantly induce apoptosis in HCT-116 cells and arrest cell cycle at the G2/M phase.
- El-Zahabi, Mohamed Ayman,Sakr, Helmy,El-Adl, Khaled.,Zayed, Mohamed,Abdelraheem, Adel S.,Eissa, Sally I.,Elkady, Hazem,Eissa, Ibrahim H.
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- Synthesis and biological evaluation of 3-amino-1,2,4-triazole derivatives as potential anticancer compounds
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Two series of compounds carrying 3-amino-1,2,4-triazole scaffold were synthesized and evaluated for their anticancer activity against a panel of cancer cell lines using XTT assay. The 1,2,4-triazole synthesis was revisited for the first series of pyridyl derivatives. The biological results revealed the efficiency of the 3-amino-1,2,4-triazole core that could not be replaced and a clear beneficial effect of a 3-bromophenylamino moiety in position 3 of the triazole for both series (compounds 2.6 and 4.6) on several cell lines tested. Moreover, our results point out an antiangiogenic activity of these compounds. Overall, the 5-aryl-3-phenylamino-1,2,4-triazole structure has promising dual anticancer activity.
- Benhida, Rachid,Demange, Luc,Dufies, Maeva,Grytsai, Oleksandr,Hagege, Anais,Martial, Sonia,Pagès, Gilles,Penco-Campillo, Manon,Ronco, Cyril,Valiashko, Oksana
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- Pyridine triazole modified coumarin Cu2 + The preparation method of the fluorescent probe (by machine translation)
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Pyridine triazole modified coumarin Cu2 + fluorescent probe preparation method, the invention relates to a triazole modified coumarin Cu pyridine2 + Fluorescent probe is 3 - formyl - 7 - (diethylamino) coumarin Schiff base, the preparation method comprises preparing a compound (A), compound (B) and compound (C) 3 - formyl - 7 - (diethylamino) coumarin Schiff base three steps. 3 - Formyl - 7 - (diethylamino) coumarin Schiff base as a fluorescent probe in the detection of copper, has good light stability, high fluorescence quantum yield, storck large displacement and the like, can be fast, efficient, single-minded identification in an aqueous solution of copper ion, which is a fast high sensitivity fluorescence probe, other common metal ion has a stronger anti-interference capability, real-time monitoring and detecting the stability is high, can be used for qualitative, quantitative detection environment in the copper ion, to the cupric ion detection has very good application value. The reaction of the invention easy control of the condition, the operation is convenient, and the yield is high. (by machine translation)
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Paragraph 0014; 0036; 0041; 0044; 0049; 0053; 0056
(2019/04/17)
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- Synthesis and anti-endoplasmic reticulum stress activity of N-substituted-2-arylcarbonylhydrazinecarbothioamides
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Misfolded or unfolded proteins are accumulated in lumen of endoplasmic reticulum (ER) in ER stress condition. It has been implicated in many pathological conditions such as Alzheimer’s disease, diabetic retinopathy, atherosclerosis, β-cell apoptosis and lung inflammation. We found a series of N-substituted-2-arylcarbonylhydrazinecarbothioamides to potently decrease ER stress signal, showing up to almost 300-fold better activity than 1-hydroxynaphthoic acid and tauro-ursodesoxycholic acid, positive controls, respectively. Structure?activity relationship (SAR) study showed that 2-arylcarbonyl moiety is critical for the activity of the hydrazinecarbothioamide analogues and side chains tethering on thioamide moiety were relatively insensitive to the activity. Some analogues were found to consistently exert the potency under more physiologically relevant condition where ER stress was induced by palmitic acid. ER stress markers such as CHOP and phosphorylated eIF2α and PERK were accordingly decreased in western blotting upon treatment of compound 4h. Potential ER stress inhibitory activity and novel structures could provide a novel platform for new chemical chaperone and therapy for protein misfolding diseases.
- Choi, Hoon,Yun, Wheesahng,Lee, Jung-hun,Jang, Seoul,Park, Sang Won,Kim, Dong Hwan,Seon, Kyoung Pyo,Hyun, Jung-mi,Jeong, Kwiwan,Ku, Jin-mo,Nam, Tae-gyu
-
p. 2142 - 2152
(2019/11/03)
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- Synthesis, in vitro screening and docking studies of new thiosemicarbazide derivatives as antitubercular agents
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A series of thiosemicarbazide derivatives was designed and synthesized by reaction of carboxylic acid hydrazide with isothiocyanates. The molecular structures of the investigated thiosemicarbazides were confirmed and characterized by spectroscopic analysis. The conformational preference of carbonylthiosemicarbazide chain and intra- and intermolecular interactions in the crystalline state were characterized using X-ray analysis. The antituberculosis activity of the target compounds were tested in vitro against four Mycobacterium strains: M. H37Ra, M. phlei, M. smegmatis, M. timereck. The most active compounds were those with 2-pyridine ring. They exhibited lower minimal inhibitory concentration (MIC) values in the range 7.81–31.25 μg/mL in comparison to the other isomers. Compound 5 had activity against M. smegmatis at a concentration of 7.81 μg/mL whereas compound 2 had activity against all tested strains at a concentration of 15.625 μg/mL. The molecular docking studies were performed for investigated compounds using the Mycobacterium tuberculosis glutamine synthetase MtGS as their molecular target.
- Pitucha, Monika,Karczmarzyk, Zbigniew,Swatko-Ossor, Marta,Wysocki, Waldemar,Wos, Maciej,Chudzik, Kamil,Ginalska, Grazyna,Fruzinski, Andrzej
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- Synthesis of novel indole derivatives containing double 1,3,4-oxadiazole moiety as efficient bactericides against phytopathogenic bacterium Xanthomonas oryzae
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Abstract: A series of novel indole derivatives containing double 1,3,4-oxadiazole moiety was designed, synthesized and evaluated for their antibacterial activities in vitro. These compounds were fully characterized by 1H NMR, 13C NMR, and HRMS. Bioassay results indicated that most of title compounds exhibited excellent antibacterial activities against rice bacterial pathogen Xanthomonas oryzae (Xoo). For example, compounds 7d, 7h, 7i, 7j, 7k, 7l and 7m had the half-maximal effective concentration (EC50) values of 52.31, 54.12, 40.65, 38.80, 51.13, 52.75 and 50.66?μg/mL, respectively, which was better than that of commercial product bismerthiazol (BMT) (85.18?μg/mL). The experimental results proved that indole derivatives bearing double 1,3,4-oxadiazole unit are promising candidates for the development of new agricultural bactericides against pathogenic bacterium Xoo. Graphical abstract: [Figure not available: see fulltext.].
- Tian, Kun,Li, Xiao-Qin,Zhang, Li,Gan, Yi-Yuan,Meng, Jiao,Wu, Shou-Qun,Wan, Jin-Lin,Xu, Yang,Cai, Chao-Ting,Ouyang, Gui-Ping,Wang, Zhen-Chao
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- Development of novel liver?X?receptor modulators based on a 1,2,4-triazole scaffold
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Liver X Receptor (LXR) agonists have been reported as a potential treatment for atherosclerosis, Alzheimer's disease and hepatitis C virus (HCV) infection. We have designed and synthesized a series of potent compounds based on a 1,2,4-triazole scaffold as novel LXR modulators. In cell-based cotransfection assays these compounds generally functioned as LXR agonists and we observed compounds with selectivity towards LXRα (7-fold) and LXRβ (7-fold) in terms of potency. Assessment of the effects of selected compounds on LXR target gene expression in HepG2 cells revealed that compounds 6a-b and 8a-b behaved as inverse agonists on FASN expression even though they were agonists in the LXRα and LXRβ cotransfection assays. Interestingly, these compounds had no effect on the expression of SREBP-1c confirming a unique LXR modulator pharmacology. Molecular docking studies and evaluation of ADME properties in-silico show that active compounds possess favorable binding modes and ADME profiles. Thus, these compounds may be useful for in vivo characterization of LXR modulators with unique profiles and determination of their potential clinical utility.
- Goher, Shaimaa S.,Griffett, Kristine,Hegazy, Lamees,Elagawany, Mohamed,Arief, Mohamed M.H.,Avdagic, Amer,Banerjee, Subhashis,Burris, Thomas P.,Elgendy, Bahaa
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supporting information
p. 449 - 453
(2019/01/04)
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- Hydrazide compounds
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The invention discloses hydrazide compounds. The compounds are characterized by having a structure represented by a formula I shown in the description, wherein Ar1 and Ar2 are each independently selected from the group consisting of aryl, azinyl, piperazinyl, pyrazolyl, imidazolyl, pyrrolyl, phenyl, naphthyl, thiazolyl, thienyl, furyl, aryl, phenyl, piperazinyl, piperidinyl, piperazinyl, and-C13H9represented by a formula 9 shown in the description, only one of the Ar1 and the Ar2 is phenyl, the Ar1 has m substituents R1, Ar2 has n substituents R2, m=0 to 3, and n=0 to 3; and if the formula Ihas a plurality of substituents R1 and R2, the plurality of substituents R1 and R2 are independent with one another, can select the same substituents or different substituents, and the R1 and the R2 are each independently selected from the group consisting of halogen, hydroxyl, cyano, C1-C3 alkyl, C1-C3 alkoxy, amino, C1-C3 alkyl substituted amino, C1-C3 alkyl disubstituted amino, perfluoro C1-C3alkyl and fluoro substituted C1-C3 alkoxy.
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-
Paragraph 0088; 0100; 0102; 0103
(2019/10/01)
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- Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine N-benzylpiperidine fragments
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Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62 nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.
- Zhou, Yeheng,Sun, Wei,Peng, Jiale,Yan, Hui,Zhang, Li,Liu, Xingyong,Zuo, Zhili
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supporting information
(2019/10/08)
-
- Synthesis method of nicotinoyl hydrazone Schiff base compound as well as application of compound to bactericide
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The invention relates to a synthesis method of a nicotinoyl hydrazone Schiff base compound as well as application of the compound to bactericide, and relates to the technical field of organic synthesis. The synthesis method of the nicotinoyl hydrazone Schiff base compound comprises two steps of synthesizing an intermediate nicotinoylhydrazine and synthesizing a target product, wherein the nicotinoylhydrazine is prepared by carrying out a refluxing stirring reaction among raw materials such as hydrazine hydrate, ethyl nicotinate and absolute ethanol, carrying out a reaction under the conditionof 80 DEG C for synthesis, and performing aftertreatment; the target product is prepared by performing refluxing stirring reaction on the prepared intermediate nicotinoylhydrazine as well as a small amount of glacial acetic acid and aldehyde compound under the condition of 65 DEG C, performing suction filtration and performing recrystallization. The synthesis reaction is simple to operate and theyield of products is high; furthermore, the synthesis method is low in equipment requirement, low in production cost and easy in industrialized large-scale application. In addition, the synthesized nicotinoyl hydrazone Schiff base compound can serve as the bactericide to selectively kill germs, and the prevention effect on wheat powdery mildew can reach to 83.1 percent.
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-
Paragraph 0033-0035; 0049; 0063; 0076
(2018/12/13)
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- Tyrosinase and carbonic anhydrase enzymes inhibition studies of vanadium(V) complexes
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Present study endeavors synthesis of series of vanadium(V) hydrazide complexes and its enzyme inhibition studies. Octahedral structure of complexes has been evaluated previously using conductance measurements, spectroscopic techniques involving IR,1H-NMR and13C-NMR, elemental analysis using CHN technique. Complexes 1c-12c have found to exhibit monomeric form with hydrazides behaving as bidentate ligand coordinating by their N and O atoms, while two oxygen atoms have also been found to show attachment with the metal centre. This study includes activity of vanadium(V) complexes to inhibit tyrosinase and carbonic anhydrase enzymes. For inhibition of carbonic anhydrase all, while for tyrosinase most of the hydrazide ligands were found to be inactive. Vanadium(V) complexes with these hydrazides have found to bear variable degree of carbonic anhydrase and tyrosinase inhibition activity. Some of the vanadium(V) hydrazide complexes were found to be potent inhibitors of tyrosinase enzyme and carbonic anhydrase as well.
- Sultan, Sadaf,Ashiq, Uzma,Jamal, Rifat Ara,Mahroof-Tahir, Mohammad,Ahmad, Rao Saeed,Shaikh, Zara
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- 3. 6 - Disubstituted [1, 2, 4] triazolo [3, 4 - b] [1, 3, 4] thiadiazole compound and use thereof
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The invention discloses 3,6-disubstituted[1,2,4]triazolyl[3,4-b][1,3,4]thiadiazole compounds represented by general formula (I), and pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof. The compounds can be used as a transpeptidase SrtA inhibitor of Staphylococcus aureus, Bacillus pyogenes, Bacillus anthracis, Streptococcus pneumoniae and other Gram-positive bacteria, and can be used to prepare drugs for treating pathogen infection diseases with the transpeptidase SrtA of the Gram-positive bacteria, such as Staphylococcus aureus, Bacillus pyogenes, Bacillus anthracis and Streptococcus pneumoniae as target. The compounds avoid selection pressure induced drug resistance of pathogens to a certain degree, and mitigate threat of continuous drug-resistant pathogens to the health of human.
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Paragraph 0071; 0072
(2018/11/22)
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- 3 - (1, 3, 4 - Oxadiazolyl) - 5 - phenoxy - pyridine derivative and its preparation method and application
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The invention discloses a new compound 3-(1, 3, 4-oxadiazol)-5-phenoxy-pyridine derivative, a preparation method and application thereof. The structural formula of the compound is shown as formula I, wherein R1 is H, or R1 can be one or more of the following monosubstituted or polysubstituted groups on benzene ring: fluorine, chlorine, bromine, methyl, methoxy, hydroxyl, nitro, amino, acetylamino, trifluoromethyl and cyano; R2 can be pyridyl, furyl, thienyl, and acylamino; under the circumstance of R3=H, R4=NH2 and R3=NH2, R4=H or R3=R4=H; X is O or S or NH or NCH3. The compound provided by the invention has good antitumor activity, and can be used as a therapeutic agent for tumor treatment in the field of anti-tumor drug preparation. (formula I).
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-
Paragraph 0032; 0033; 0034
(2018/03/25)
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- Coumarin nicotinic hydrazide schiff base Al fluorescent probe preparation method and application thereof
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The invention relates to the field of a fluorescent probe, and especially relates to a coumarin nicotinic hydrazide schiff base Al fluorescent probe preparation method and an application thereof.A concrete structural formula is shown as the description, the fluorescent probe can identify Al in an EtOH-H2O (95:5,v/v, HEPES 20mmol/L, pH is 7.20) solution, and the preparation method has theadvantages that the fluorescent probe presents excellent selectivity in competition with other ions, and has high fluorescence sensing property, the detection limit is low, the detection sensitivity is high, and the fluorescence quantum yield is high.
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Paragraph 0031; 0036; 0037; 0038; 0039
(2018/09/21)
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- Structure-Guided Synthesis and Mechanistic Studies Reveal Sweetspots on Naphthyl Salicyl Hydrazone Scaffold as Non-Nucleosidic Competitive, Reversible Inhibitors of Human Ribonucleotide Reductase
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Ribonucleotide reductase (RR), an established cancer target, is usually inhibited by antimetabolites, which display multiple cross-reactive effects. Recently, we discovered a naphthyl salicyl acyl hydrazone-based inhibitor (NSAH or E-3a) of human RR (hRR) binding at the catalytic site (C-site) and inhibiting hRR reversibly. We herein report the synthesis and biochemical characterization of 25 distinct analogs. We designed each analog through docking to the C-site of hRR based on our 2.7 ? X-ray crystal structure (PDB ID: 5TUS). Broad tolerance to minor structural variations preserving inhibitory potency is observed. E-3f (82% yield) displayed an in vitro IC50 of 5.3 ± 1.8 μM against hRR, making it the most potent in this series. Kinetic assays reveal that E-3a, E-3c, E-3t, and E-3w bind and inhibit hRR through a reversible and competitive mode. Target selectivity toward the R1 subunit of hRR is established, providing a novel way of inhibition of this crucial enzyme.
- Huff, Sarah E.,Mohammed, Faiz Ahmad,Yang, Mu,Agrawal, Prashansa,Pink, John,Harris, Michael E.,Dealwis, Chris G.,Viswanathan, Rajesh
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supporting information
p. 666 - 680
(2018/02/16)
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- Synthesis and pharmacological evaluation of pyridinyl-1,3,4-oxadiazolyl-ethanone derivatives as antimicrobial, antifungal and antitubercular agents
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Abstract: Nicotinic acid was converted into different substituted acetylated nicotinic acid derivatives by sequential transformation involving formation of hydrazide, Schiff’s base and finally acylated oxadiazole derivatives. The synthesized compounds were characterized by spectroscopic techniques and evaluated in vitro for the antimicrobial, antifungal, as well as antitubercular activity. Among all the synthesized derivatives, compounds 6b, 6d, 6e, 6g, and 6j demonstrated excellent antimicrobial activity on Bacillus subtilis. The compounds 6d, 6j and compounds 6b, 6f, 6h, and 6i exhibited maximum zone of inhibition against fungi Candida albicans as well as Aspergillus niger, respectively at the concentration of 500 μg/mL. The antitubercular activity exhibited by 6f, 6g, and 6d with minimum inhibitory concentration (MIC) values of 1.2, 3.1, and 7.8 μg/mL, respectively. The synthesized compounds were studied by molecular docking through Autodock Vina to evaluate their interaction at respective proteins. Further the effect of synthesized derivatives on surface morphology of human erythrocytes as well as hemolysis was also evaluated. The results demonstrated lesser extent of hemolytic toxicity.
- Mansoori, Mohammad Hashim,Khatik, Gopal L.,Mishra, Vijay
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p. 744 - 755
(2017/10/30)
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- HISTONE DEACETYLASE INHIBITORS AND USES THEREOF
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Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of cancer.
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Page/Page column 22; 23; 24
(2018/04/27)
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- Method for preparing aminopyridine from methylpyridine, and purifying method of aminopyridine
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The invention relates to the field of organic synthesis, and concretely relates to a method for preparing aminopyridine from methylpyridine, and a purifying method of aminopyridine. Crude aminopyridine is prepared from corresponding methylpyridine through oxidation, esterification, hydrazinolysis and rearrangement reactions, the reaction yield of every step is high, and a post-treatment technology is easy to industrially operate; in the oxidation reaction, beta-cyclodextrin is used as a catalyst, so the conversion rate of the oxidation reaction is increased, and the generation of byproducts is reduced; and anhydrous ethanol and an alkane reagent are used to re-crystallize the crude aminopyridine, and a decolorizing agent is combined, and the purity of the final product reaches 98% or more; and the purifying method has the advantages of simplicity, easiness in operation, easily available raw materials, and suitableness for industrial production.
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Paragraph 0031
(2017/09/01)
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- Heterocycles 39. Synthesis, characterization and evaluation of the anti-inflammatory activity of thiazolo[3,2-b][1,2,4]triazole derivatives bearing pyridin-3/4-yl moiety
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Abstract: A series of pyridin-3/4-yl-thiazolo[3,2-b][1,2,4]triazole derivatives (5a–g, 6a–g) were synthesised by Hantzsch condensation of 5-pyridin-3/4-yl-1,2,4-triazole-3-thiol and diverse α-halocarbonyl compounds. Different reaction conditions (pH, temperature, solvent) were investigated for the efficient obtention of the target compounds. Under reflux and acidic conditions, the Hantzsch condensation was a one-step reaction. At room temperature and under basic conditions, it was possible to isolate the iminothioether intermediates 3/4a–g. These intermediates were cyclized in a subsequent step by treatment with concentrated sulphuric acid. The obtained compounds were evaluated for their anti-inflammatory activity. Three synthesised pyridyl-thiazolo[3,2-b][1,2,4]triazole derivatives (6c, 6d, 6f) were found to be good anti-inflammatory agents. Graphical Abstract: [InlineMediaObject not available: see fulltext.].
- Toma, Alexandra,Mogo?an, Cristina,Vlase, Laurian,Leonte, Denisa,Zaharia, Valentin
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p. 2602 - 2613
(2017/10/06)
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- Synthesis, spectral analysis and antibacterial evaluation of 5-substituted-1,3,4-oxadiazol-2-yl 4-(4-methylpiperidin-1-ylsulfonyl)benzyl sulfides
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Owing to valuable biological activities of 1,3,4-oxadiazole, sulfamoyl and piperidine functionalities, some new 1-(4-{[(5-substituted-1,3,4-oxadiazol-2-yl) thio]methyl}benzene sulfonyl)-4-methylpiperidine (6a-o) derivatives have been introduced. The target molecules were synthesized from different aralkyl/aryl carboxylic acids, 1a-o, through a series of steps. First the compounds, 1a-o, were converted to heterocyclic 1,3,4-oxadiazole nucleophiles, 4a-o. Second an electrophile as 1-(4-bromomethylbenzenesulfonyl)-4-methylpiperidine (5) was synthesized from 4-methylpiperidine. Finally the target compounds, 6a-o, were prepared by reacting 4a-o with 5 in DMF and LiH. The final compounds were structurally elucidated by spectral data of IR, 1H-NMR and EI-MS. All the compounds were screened for their antibacterial evaluation and found to exhibit valuable results.
- Aziz-Ur-Rehman,Ahtzaz, Samreen,Abbasi, Muhammad Athar,Siddiqui, Sabahat Zahra,Rasool, Shahid,Ahmad, Irshad
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p. 3370 - 3375
(2017/05/22)
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- THERMAL VOLATILIZATION OF ORCO AGONISTS
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In one aspect, the invention relates to chemical modulators of insect olfactory receptors. In particular, compounds and compositions are provided that can inhibit sensory (e.g., host targeting) functions in airborne insects such as mosquitos. Method of employing such agents, and articles incorporating the same, are also provided. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 00473
(2017/02/09)
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- Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents
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Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100?μg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.
- Sonawane, Amol D.,Rode, Navnath D.,Nawale, Laxman,Joshi, Rohini R.,Joshi, Ramesh A.,Likhite, Anjali P.,Sarkar, Dhiman
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p. 200 - 209
(2017/07/13)
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- Pyridine methylamino dithio formic acid heteroaryl naphthenic base ester compound and preparation method and application thereof
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The invention relates to a compound as shown in a general formula (I) or pharmaceutically acceptable salts or solvates thereof, and relates to a preparation method of the compound and application thereof in preparing anti-tumor drugs. Please see the general formula (I) in the description.
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Paragraph 0167; 0168; 0169; 0223; 0224; 0225
(2017/01/02)
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- Synthesis and biological evaluation of novel hydrogen sulfide releasing nicotinic acid derivatives
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Twelve novel hybrids of slowly releasing hydrogen sulfide donor ADT-OH combined with nicotinic acid were synthesized. All of their structures had been confirmed by1H NMR,13C NMR and MS spectra. The target compounds were evaluated for their neuroprotective effects on hippocampal neuron HT22 cells against glutamate-induced injury at the concentrations of 1–100?μM with MTT assay, and their toxicity on HT22 cells untreated by glutamine at the concentration of 100?μM. The active compound was further investigated for its effect on ischemic infarct volume by intraperitoneal injection at 3?h after ischemia in mice models of permanent middle cerebral artery occlusion (pMCAO). The results showed that all the compounds significantly protected HT22 cells from glutamate-induced damage at most of the experimental concentrations, and had no or little neurotoxicity on normal HT22 cells at the high concentration. More importantly, compound A6 significantly reduced infarct volume in the pMCAO model. These results suggested that compound A6 may be promising for further evaluation for the intervention of cerebral ischemic injury.
- Sun, Yinxing,Zhang, Yusuo,Li, Yuyao,Cheng, Jian,Chen, Shiyu,Xiao, Yunqi,Ao, Guizhen
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p. 5368 - 5373
(2016/10/24)
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- NOVEL PYRIDINIUM COMPOUNDS
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The present invention relates to novel pyridinium compounds, their isomers, steroisomers, atropisomers, conformers, tautomers, polymorphs, hydrates and solvates. The present invention also encompasses process for preparing novel compounds and pharmaceutical composition of said compounds. The invention further relates to the use of the above mentioned compounds for the preparation of medicament for use as pharmaceuticals.
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Page/Page column 22
(2016/10/31)
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- Acylhydrazone derivative used for treating heart failure
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The invention belongs to the technical field of medicines, and relates to design and preparation method for acylhydrazone derivatives shown as a general formula I, and the acylhydrazone derivatives can be used for treating systolic heart failure comprising congestive heart failure.
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-
Paragraph 0036; 0037; 0038
(2016/10/08)
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- 1,2,4-TRIAZOLE, 1,3,4-OXADIAZOLE, AND 1,3,4-THIADIAZOLE DERIVATIVES AND THEIR ANTIMYCOBACTERIAL ACTIVITY
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Disclosed herein are novel five membered heterocyclic compounds of Formula (I) wherein, X is S or SO2; n is 0, 1; m is1 or 2; Y is N, O or S; R2 independently represents H or alkyl or halo selected from -CI, -F; or -CF3, or -OH or-NH2 or - NO2; and R1 independently represents H or C1 to C5 straight or branched chain alkyl, alkenyl, alkynyl or a group -(CH2)5Br or pyrrolidine or - NHR' wherein R' is H or isopropyl or (II) or (III) which selectively act against dormant pathogenic tuberculi bacilli and exhibit antiproliferative activities and for treatment of a disease or disorder associated with GroEL1/GroEL2 activity. The invention relates to a process for preparation of novel five membered heterocyclic compounds of Formula I and to pharmaceutical compositions thereof.
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Paragraph 054
(2016/07/27)
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- Synthesis, antibacterial and antiproliferative potential of some new 1-pyridinecarbonyl-4-substituted thiosemicarbazide derivatives
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In this study, the antibacterial, cytotoxic and antiproliferative activities of novel thiosemicarbazide derivatives were assessed. Our results demonstrated that some of the novel compounds possess good antibacterial properties against Staphylococcus epidermidis, Streptococcus mutans and Streptococcussanguinis and are only slightly cytotoxic; thus, they exhibit an excellent therapeutic index, which is higher than that of ethacridine lactate. Moreover, our data showed that compounds 2 and 4 have an antiproliferative activity against human breast adenocarcinoma and human hepatocellular carcinoma cell lines. We expect that the novel thiosemicarbazide derivatives can be used as agents for treatment of dental caries and also for chemotherapy support.
- Pitucha, Monika,Wo?, Maciej,Miazga-Karska, Malgorzata,Klimek, Katarzyna,Miros?aw, Barbara,Pachuta-Stec, Anna,G?adysz, Agata,Ginalska, Grazyna
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p. 1666 - 1677
(2016/07/30)
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- Synthesis and biological activities of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors
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A series of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases have been conveniently synthesized in good yields. Their structures were characterized by IR,1H NMR,13C NMR and elemental analysis. The preliminary bioassay results indicated that some of the compounds showed promising in vitro fungicidal activities towards several test plant fungi; some of them exhibited significant herbicidal activities against Brassica campestris and excellent in vitro inhibitory activities against rice ketol-acid reductoisomerase (KARI). Among 14 novel compounds, 8c, 8d and 8m showed potent KARI inhibitory activities with Kivalue of (0.96?±?0.42), (3.86?±?0.49) and (3.10?±?0.71) μmol/L, respectively, and were comparable with IpOHA. These compounds could be novel KARI inhibitors for further investigation. The density functional theory (DFT) calculations and molecular docking were carried out to study the structure–activity relationship (SAR) of the active inhibitors in this Letter.
- Zhang, Yan,Liu, Xing-Hai,Zhan, Yi-Zhou,Zhang, Li-Yuan,Li, Zheng-Ming,Li, Yong-Hong,Zhang, Xiao,Wang, Bao-Lei
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supporting information
p. 4661 - 4665
(2016/09/13)
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- Development of Allosteric Hydrazide-Containing Class i Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia
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One of the biggest hurdles yet to be overcome for the continued improvement of histone deacetylase (HDAC) inhibitors is finding alternative motifs equipotent to the classic and ubiquitously used hydroxamic acid. The N-hydroxyl group of this motif is highly subject to sulfation/glucoronidation-based inactivation in humans; compounds containing this motif require much higher dosing in clinic to achieve therapeutic concentrations. With the goal of developing a second generation of HDAC inhibitors lacking this hydroxamate, we designed a series of potent and selective class I HDAC inhibitors using a hydrazide motif. These inhibitors are impervious to glucuronidation and demonstrate allosteric inhibition. In vitro and ex vivo characterization of our lead analogues' efficacy, selectivity, and toxicity profiles demonstrate that they possess low nanomolar activity against models of acute myeloid leukemia (AML) and are at least 100-fold more selective for AML than solid immortalized cells such as HEK293 or human peripheral blood mononuclear cells.
- McClure, Jesse J.,Zhang, Cheng,Inks, Elizabeth S.,Peterson, Yuri K.,Li, Jiaying,James Chou
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p. 9942 - 9959
(2016/11/19)
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