- Barbiturate bearing aroylhydrazine derivatives: Synthesis, NMR investigations, single crystal X-ray studies and biological activity
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A series of barbituric acid aroylhydrazine derivatives have been prepared from their corresponding 1,3-dimethyl-5-acetyl barbituric acid and aroylhydrazines. All compounds have been fully characterized by using FT-IR, multinuclear NMR (1H, 13C) and Mass (MS) spectrometry. We also describe the X-ray crystal structure of 3a, which crystallizes in the monoclinic P21/n space group. The crystal structure is stabilized with infinite linear chains of dimeric units. Furthermore, all compounds were investigated for their tyrosinase inhibition, antioxidative and antimicrobial activies. The results from biological activity assays have shown that all of compounds have excellent antioxidant, significant tyrosinase inhibition and moderate antimicrobial activity.
- Giziroglu, Emrah,Sarikurkcu, Cengiz,Aygün, Muhittin,Basbulbul, Gamze,Soyleyici, H. Can,Firinci, Erkan,Kirkan, Bulent,Alkis, Ayse,Saylica, Tayfur,Biyik, Halil
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- Oxidative cyclocondensation of thio(seleno)-amides and ureas 1. 2-thioxo-4-quinazolone
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It has been found for the first time that 2-thioxo-4-quinazolone in the presence of acid catalysts in dimethyl sulfoxide is converted to 8H,15H-1,2,4-thiadiazolo[3, 2-b:5, 4-b′]diquinazoline-8, 15-dione. The reaction proceeds via oxidative cyclocondensation. The formation of this structure in preference to five other proposed isomers is substantiated using quantum-chemical methods. 1997 Plenum Publishing Corporation.
- Shakhidoyatov,Urakov,Mukarramov,Ashirmatov,Bruskov
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- Synthesis and characterization of novel M(II) (M = Mn(II), Ni(II), Cu(II) or Zn(II)) complexes with tridentate N2, O-donor ligand (E)-2-amino-N'-[1-(pyridin-2-yl)ethylidene]benzohydrazide
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The coordination chemistry towards the M(II) metal centre (M = Mn, Ni, Cu or Zn) of the hydrazone ligand (E)-2-amino-N'-[1-(pyridin-2-yl)ethylidene]benzohydrazide (H3L) has been explored and complexes having formulae [Mn(H2L)2] (1), {[Ni(H2L)2].DMF.0.4H2O} (2), {[Cu2(H2L)2(μ-Cl)2].DMF} (3) and [Zn(H2L)2] (4) have been isolated and characterized by IR, UV-Visible spectroscopy, elemental analysis and Xray crystal diffraction. Structural studies reveal that the mononuclear complexes (1), (2) and (4) adopt highly distorted octahedral geometries while the dinuclear complex (3) adopts a square pyramidal geometry around each copper(II) ion.
- Kane, Cheikh Hamidou,Tinguiano, Daniel,Tamboura, Farba Bouyagui,Thiam, Ibrahima Elhadj,Barry, Aliou Hamady,Gaye, Mohamed,Retailleau, Pascal
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- A novel nitrogen heterocycle platform-based highly selective and sensitive fluorescence chemosensor for the detection of Al3+ and its application in cell imaging
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In the study, a highly selective and sensitive fluorescence sensor derived from nitrogen heterocycle was synthesized and characterized. By the fluorescence experiments, it was found to show a higher response toward Al3+ than other commonly coexistent metal ions in C2H5OH/H2O media (pH = 7.2). Moreover, the large binding constant (3.44 × 1014 M-1) between Al3+ and the sensor was calculated by fluorescence titration experiment. In addition, the synergistic effect mechanism due to photoinduced electron transfer (PET) and CN isomerization was deduced according to the fluorescence behavior. In addition, the fluorescence imaging in living cells was studied systemically, which exhibited high fluorescence sensing activity toward Al3+.
- Liu, Zengchen,Li, Shujing,Ge, Genwu,Li, Yanxia,Zhao, Chunxiang,Zhang, Hui,Yang, Zhiguang
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- Room-temperature switching of magnetic hysteresis by reversible single-crystal-to-single-crystal solvent exchange in imidazole-inspired Fe(II) complexes
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The recent upsurge in molecular magnetism reflects its application in the areas of sensors and molecular switches. Thermal hysteresis is crucial to the molecular bistability and information storage, a wide hysteresis near room temperature is expected to be of practical sense for the molecular compound. In this work, spin crossover iron(ii) complexes [Fe(Liq)2](BF4)2·(CH3CH2)2O (1-Et2O) and [Fe(Liq)2](BF4)2·3H2O (1-3H2O) were prepared and structurally and magnetically analysed. The single-crystal-to-single-crystal (SCSC) solvation transformation and the influence on the crystal structures and magnetic hysteresis were investigated in an etherification-hydration cycle. At room temperature, X-ray diffraction experiments indicated a transformation from one crystal (1-Et2O, P21212) to another crystal (1-3H2O, P212121) upon humidity exposure and reversible recovery of its crystallinity upon exposure to ether vapor. The etherified phase 1-Et2O exhibits room temperature spin crossover (T1/2 = 305 K) but negligible thermal hysteresis, however the hydrated phase 1-3H2O exhibits the apparent hysteresis loop (T1/2↑ = 346 K, T1/2↓ = 326 K) which expands to room temperature. This effect is associated with the change of intermolecular cooperativity in the etherification-hydration recyclability.
- Huang, Wei,Shen, Fuxing,Zhang, Ming,Wu, Dayu,Pan, Feifei,Sato, Osamu
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- Synthesis and anti-microbial / anti-malarial activity of a new class of chromone-dihydroquinazolinone hybrid heterocycles
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A new series of chromone-2,3-dihydroquinazolin-4-one hybrid heterocycles are synthesized from chromone-2-carbaldehydes by coupling with 2-Aminoarylamides and hydrazides without oxidizing agents. The newly synthesized products exhibited moderate to good antimicrobial activity.
- Bathini, Pavan Kumar,Yerrabelly, Hemasri,Yerrabelly, Jayaprakash Rao
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- Synthesis, spectral characterization and thermal studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with 2-amino benzoic acid- and 2-hydroxy benzoic acid thiophen-2-ylmethylene hydrazide
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A series of metal complexes of Co(II), Ni(II), Cu(II) and Zn(II) with 2-amino benzoic acid thiophen-2-ylmethylene hydrazide (Habth) and 2-hydroxy benzoic acid thiophen-2-ylmethylene hydrazide (Hhbth) have been synthesized. The complexes were characterized by elemental analyses, molar conductance, magnetic susceptibility measurements, electronic, IR, NMR, ESR spectra and thermal studies (TGA and DTA). Molecular structure of the Habth ligand was determined by single crystal X-ray diffraction technique. Habth acts as a monobasic bidentate ligand in all its complexes bonding through a deprotonated CO- and CN groups whereas, Hhbth acts as a monobasic bidentate in its Co(II) and Ni(II) complexes, bonding through a deprotonated CO- and CN groups and as monobasic tridentate in Cu(II) and Zn(II) complexes bonding through CO, CN and deprotonated (CO)- groups with the metal ion. Electronic spectra suggest a square planar geometry for Co(II), Ni(II) and Cu(II) complexes of Habth and Co(II) and Ni(II) complexes of Hhbth. However, the Cu(II) and Zn(II) complexes of Hhbth have octahedral geometry. The ESR spectra of Cu(II) complex of Hhbth in the solid state and in DMSO frozen solution show axial signals and suggest the presence of unpaired electron in dx2-y2 orbital of Cu(II). The Cu(II) complex of Habth in solid state shows isotropic signal, whereas, axial signal in DMSO frozen solution in the range of tetragonally distorted octahedral geometry due to interactions of DMSO molecules at axial positions. Thermal studies of some of the metal complexes show a multi-step decomposition pattern of bonded ligands in the complex.
- Singh, Vinod P.,Singh, Pooja
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- Synthesis, physicochemical, and biological studies of complexes of 2-Aminobenzohydrazine with Co(II), ni(II), Cu(II), and zn(II) chlorides
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Coordination complexes of modified hydrazine bearing unit were synthesized with transition metals viz. Cu(II), Co(II), Ni(II), and Zn(II). The ligand amino benzohydrazide (ABH) was synthesized by replacing the methoxy moiety of methyl anthranilate with the nitrogen of the hydrazine hydrate, creating new coordination site. The coordination complexes were made by the reaction of ABH ligand with dehydrated metal chloride in inert environment. The compositions and structures of ligand and coordination complexes were elucidated employing physical measurements such as microanalysis, NMR, IR, UV-visible spectroscopy, magnetic, and conductance measurements. The results revealed the composition as M(ABH)Cl2. All of them exhibited tetrahedral geometry. Thermal studies of these metal complexes reveal the Irving William series trend regarding their stabilities. Antibacterial and antifungal inhibitions were also tested in order to determine the effectiveness of these complexes. Copyright Taylor & Francis Group, LLC.
- Ikram, Muhammad,Rehman, Sadia,Ullah, Farhat,Akhtar, Gul
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- Pyridazino[1,6-b]quinazolinones as new anticancer scaffold: Synthesis, DNA intercalation, topoisomerase I inhibition and antitumor evaluation in vitro and in vivo
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A new anticancer N-containing heterocyclic scaffold was designed and 30 pyridazino[1,6-b]quinazolinone derivatives were synthesized and characterized. Antiproliferation evaluation in vitro against four human cancer cell lines including SK-OV-3(ovarian cell), CNE-2(nasopharyngeal cell), MGC-803(gastric cell) and NCI-H460(lung cell) indicated that most of them exhibited potent anticancer activity and the IC50 value of the most potent compound lowered to sub-μM. DNA interaction assay indicated that compounds 4e, 4g, 6o, 6p, 8o can intercalate into DNA. Compounds 6 and 8 also demonstrated potent topoisomerase I (topo I) activity. Annexin V- FITC/propidium iodide dual staining assay and cell cycle analysis indicated that 2-(4-bromophenyl)-4-((3-(diethylamino)propyl)amino) ?10H-pyridazino [1,6-b]quinazolin- 10-one (8p) could induce arrest cell cycle at G2 phase and apoptosis in MGC-803 cells in a dose-dependent manner. The in vivo antitumor efficiency of compound 8p was also evaluated on MGC-803 xenograft nude mice, and the relative tumor growth inhibition was up to 55.9% at a dose of 20 mg/kg per two days. The results suggested that pyridazino[1,6-b]-quinazolinones might serve as a promising novel scaffold for the development of new antitumor agents.
- Huang, Wan-Yun,Zhang, Xiao-Rong,Lyu, Liang,Wang, Shu-Qin,Zhang, Xiao-Ting
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- Synthesis and spectroscopic studies of mixed-ligand and polymeric dinuclear transition metal complexes with bis-acylhydrazone tetradentate ligands and 1,10-phenanthroline
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Two types of dinuclear copper(II) and nickel(II) complexes with two tetradentate N2O2 donor ligands 1,4-bis(1-anthranoylhydrazonoethyl)benzene (L1), 1,4-bis(1-salicyloylhydrazonoethyl)benzene (L2) and N,N′-bidentate heterocyclic base [1,10-phenonthroline (phen)] have been synthesized and characterized by elemental analysis, infrared spectra, UV-vis electronic absorption spectra and magnetic susceptibility measurements. The reaction of metal(II) acetates with the solution containing ligand and 1,10-phenonthroline in methanol gives mixed-ligand dinuclear metal(II) complexes with general formula [M2L(phen)2]Cl2 (L = L1 or L2), whereas, the ligands react with metal(II) acetates to form polymeric dinuclear complexes with general formula [(M2L2)n] (L = L1 or L2). In the complexes, the ligands act as dianionic tetradentate and coordination takes place in the enol tautomeric form with the enolic oxygen and azomethine nitrogen atoms while the phenolic hydroxyl and amino groups of aroylhydrazone moiety do not participate in coordination. The effect of varying pH and solvent on the absorption behavior of both ligands and complexes has been investigated.
- Gup, Ramazan,Kirkan, Buelent
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- Mononuclear late first row transition metal complexes of ONO donor hydrazone ligand: Synthesis, characterization, crystallographic insight, in vivo and in vitro anti-inflammatory activity
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Air and moisture stable coordination compounds of late first row transition metal ions, viz., Co(II), Ni(II), Cu(II) and Zn(II) with a newly designed ligand, (E)-2-amino-N'-(1-(2-hydroxy-6-methyl-4-oxo-4H-pyran-3-yl)ethylidene)benzohydrazide (H2L) were prepared and extensively characterized using various spectro-analytical techniques. The ligand acts both in mono as well as doubly deprotonated manner. The ligand to metal stoichiometry was found to be 1:2 in case of complexes using chloride salts, whereas 1:1 in case of copper (II) complex using its acetate salt. The molecular structures of H2L, nickel and copper complexes were unambiguously determined by single-crystal X-ray diffraction studies reveal that H2L exists in a zwitterionic form while copper complex has copper centre in a distorted square planar environment. On the other hand, cobalt, nickel and zinc complexes display distorted octahedral coordination around the metal ion. In case of [Ni(HL)2].H2O, intramolecular C–H?π stacking interaction were observed between the centroid of five membered chelate ring and phenyl proton C5–H5 and intermolecular C–H?π stacking interaction between the centroid of phenyl ring, dehydroacetic acid (DHA) ring and phenyl protons. The [Cu(L)DMF] complex is stabilized by intramolecular hydrogen bonding N1H?N2 and by intermolecular hydrogen bonding N1H?O4. Intermolecular interactions were investigated by Hirshfeld surfaces. Further, H2L and its metal complexes were screened for their in vivo and in vitro anti-inflammatory activities. The activity of the ligand has enhanced on coordination with transition metals. The tested compounds have shown excellent activity, which is almost equipotent to the standard used in the study.
- Kendur, Umashri,Chimmalagi, Geeta H.,Patil, Sunil M.,Gudasi, Kalagouda B.,Frampton, Christopher S.,Mangannavar, Chandrashekhar V.,Muchchandi, Iranna S.
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- Discovery of phthalazino[1,2-b]-quinazolinone derivatives as multi-target HDAC inhibitors for the treatment of hepatocellular carcinoma via activating the p53 signal pathway
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In view of histone deacetylases (HDACs) as a promising target for cancer therapy, a series of phthalazino[1,2-b]-quinazolinone units were hybrided with ortho-aminoanilide or hydroxamic acid to serve as multi-target HDAC inhibitors for the treatment of solid tumors. Among the target compounds, 8h possessed nano-molar IC50 values toward the tested cancer cells and HDAC subtypes, which was more potent than the HDAC inhibitor SAHA (vorinostat). Mechanism study revealed that compound 8h could suppress the HepG2 cell proliferation via prompting the acetylation of histone 3 (H3) and α-tubulin, and activating the p53 signal pathway as designed. In addition, compound 8h exhibited much stronger in vivo antitumor efficacy than SAHA in the HepG2 xenograft tumor model with negligible toxicity. As a novel multi-target HDAC inhibitor, compound 8h deserves further development as a potential anticancer agent.
- Liu, Qingqing,Zhang, Bin,Wang, Yuanjiang,Wang, Xinyi,Gou, Shaohua
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- Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction
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Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.
- Zhou, Wenjuan,Xu, Chenhao,Dong, Guanjun,Qiao, Hui,Yang, Jing,Liu, Hongmin,Ding, Lina,Sun, Kai,Zhao, Wen
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- Multi-target anti-tumor small molecules and their derivatives, preparation methods, pharmaceutical compositions and applications
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The present invention discloses a class of multi-target anti-tumor small molecules and derivatives thereof, preparation methods, pharmaceutical compositions and applications. The chemical structure of such small molecules as shown in formula I, the derivative of which relates to a pharmaceutically acceptable salt of the small molecule. This class of small molecules and their derivatives has a highly efficient tumor suppressor effect in vivo and abroad, low toxicity to cells and organisms, no genotoxicity; anti-tumor activity is achieved through multi-target action, with pan-HDAC inhibitory activity, and can also effectively activate the p53 pathway, inhibit topoisomerase activity, can be used to prepare anti-tumor drugs; the preparation method is simple and easy to operate.
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Paragraph 0039-0040; 0044-0046
(2022/01/05)
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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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- Discovery of an Orally Efficacious MYC Inhibitor for Liver Cancer Using a GNMT-Based High-Throughput Screening System and Structure-Activity Relationship Analysis
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Glycine-N-methyl transferase (GNMT) downregulation results in spontaneous hepatocellular carcinoma (HCC). Overexpression of GNMT inhibits the proliferation of liver cancer cell lines and prevents carcinogen-induced HCC, suggesting that GNMT induction is a potential approach for anti-HCC therapy. Herein, we used Huh7 GNMT promoter-driven screening to identify a GNMT inducer. Compound K78 was identified and validated for its induction of GNMT and inhibition of Huh7 cell growth. Subsequently, we employed structure-activity relationship analysis and found a potent GNMT inducer, K117. K117 inhibited Huh7 cell growth in vitro and xenograft in vivo. Oral administration of a dosage of K117 at 10 mpk (milligrams per kilogram) can inhibit Huh7 xenograft in a manner equivalent to the effect of sorafenib at a dosage of 25 mpk. A mechanistic study revealed that K117 is an MYC inhibitor. Ectopic expression of MYC using CMV promoter blocked K117-mediated MYC inhibition and GNMT induction. Overall, K117 is a potential lead compound for HCC- and MYC-dependent cancers.
- Kant, Rajni,Yang, Ming-Hui,Tseng, Chih-Hua,Yen, Chia-Hung,Li, Wei-You,Tyan, Yu-Chang,Chen, Marcelo,Tzeng, Cherng-Chyi,Chen, Wei-Cheng,You, Kaiting,Wang, Wen-Chieh,Chen, Yeh-Long,Chen, Yi-Ming Arthur
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p. 8992 - 9009
(2021/07/19)
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- Dithiocarbamate as a valuable scaffold for the inhibition of metallo-β-lactmases
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The ‘superbug’ infection caused by metallo-β-lactamases (MβLs) has grown into an emergent health threat. Given the clinical importance of MβLs, a novel scaffold, dithiocarbamate, was constructed. The obtained molecules, DC1, DC8 and DC10, inhibited MβLs NDM-1, VIM-2, IMP-1, ImiS and L1 from all three subclasses, exhibiting an IC50 50 0.22 μM). DC1-2, DC4, DC8 and DC10 restored antimicrobial effects of cefazolin and imipenem against E. coli-BL21, producing NDM-1, ImiS or L1, and DC1 showed the best inhibition of E. coli cells, expressing the three MβLs, resulting in a 2-16-fold reduction in the minimum inhibitory concentrations (MICs) of both antibiotics. Kinetics and isothermal titration calorimetry (ITC) assays showed that DC1 exhibited a reversible, and partially mixed inhibition, of NDM-1, ImiS and L1, with Ki values of 0.29, 0.14 and 5.06 μM, respectively. Docking studies suggest that the hydroxyl and carbonyl groups of DC1 form coordinate bonds with the Zn (II) ions, in the active center of NDM-1, ImiS and L1, thereby inhibiting the activity of the enzymes. Cytotoxicity assays showed that DC1, DC3, DC7 and DC9 have low toxicity in L929 mouse fibroblastic cells, at a dose of up to 250 μM. These studies revealed that the dithiocarbamate is a valuable scaffold for the development of MβLs inhibitors.
- Ge, Ying,Xu, Li-Wei,Liu, Ya,Sun, Le-Yun,Gao, Han,Li, Jia-Qi,Yang, Kewu
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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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- Structural design, synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents
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4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.
- Meira, Cássio S.,dos Santos Filho, José Maurício,Sousa, Caroline C.,Anjos, Pamela S.,Cerqueira, Jéssica V.,Dias Neto, Humberto A.,da Silveira, Rafael G.,Russo, Helena M.,Wolfender, Jean-Luc,Queiroz, Emerson F.,Moreira, Diogo R.M.,Soares, Milena B.P.
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p. 1971 - 1985
(2018/03/12)
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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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- Preparation and application of zinc ion fluorescence probe based on Schiff base
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The invention relates to preparation and application of a zinc ion fluorescence probe based on Schiff base. A zinc ion fluorescence probe compound has the structure shown by a formula I. The preparation method comprises the steps that 2-aminobenzoic acid (methyl anthranilate) and hydrazine hydrate are subjected to heating reflux in ethyl alcohol to obtain a white solid II, cyanophenyl phenol, anhydrous magnesium chloride and paraformaldehyde are subjected to heating reflux in a triethylamine-containing acetonitrile solution to obtain a white solid III, the white solid II and the white solid III are subjected to heating reflux in ethyl alcohol to a yellow solid I. The probe compound has very good selectivity and sensitivity on zinc ions, is low in detection limit and can be applied to determination of the content of zinc ions in a water body.
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Paragraph 0023
(2017/08/29)
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- Synthesis of new substituted 5-amino-8H-phthalazino[1,2-b]quinazolin-8-one derivatives
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A series of novel substituted 5-amino-8H-phthalazino[1,2-b]quinazolin-8-one derivatives synthesised by condensation of different amines with 5-chloro-8H-phthalazino[1,2-b]quinazolin-8-one, which was prepared from methyl 2-aminobenzoate by condensation with hydrazine hydrate and then cyclisation with a phthalic anhydride in N,N-dimethylacetamide at refluxing condition. The intermediate and target compounds were obtained in good yields and were easily purified by filtration or recrystallisation.
- Liu, Ju,Hao, Xue-Chen,Chen, Ye,Ding, Shi,Liu, Hong-Sheng,Wang, Dan
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- Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors
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A novel series of 5-(aroylhydrazinocarbonyl)escitalopram (58–84) have been designed, synthesized and tested for their inhibitory potential against cholinesterases. 3-Chlorobenzoyl- (71) was found to be the most potent compound of this series having IC50 1.80 ± 0.11 μM for acetylcholinesterase (AChE) inhibition. For the butyrylcholinesterase (BChE) inhibition, 2-bromobenzoyl- (76) was the most active compound of the series with IC50 2.11 ± 0.31 μM. Structure-activity relationship illustrated that mild electron donating groups enhanced enzyme inhibition while electron withdrawing groups reduced the inhibition except o-NO2. However, size and position of the substituents affected enzyme inhibitions.. In docking study of AChE, the ligands 71, 72 and 76 showed the scores of 5874, 5756 and 5666 and ACE of ?64.92,-203.25 and ?140.29 kcal/mol, respectively. In case of BChE, ligands 71, 76 and 81 depicted high scores 6016, 6150 and 5994 with ACE values ?170.91, ?256.84 and ?235.97 kcal/mol, respectively.
- Nisa, Mehr-un,Munawar, Munawar A.,Iqbal, Amber,Ahmed, Asrar,Ashraf, Muhammad,Gardener, Qurra-tul-Ann A.,Khan, Misbahul A.
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supporting information
p. 396 - 406
(2017/07/10)
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- Phthalazino[1,2-b]quinazolinones as p53 Activators: Cell Cycle Arrest, Apoptotic Response and Bak-Bcl-xl Complex Reorganization in Bladder Cancer Cells
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p53 inactivation is a clinically defined characteristic for cancer treatment-nonresponsiveness. It is therefore highly desirable to develop anticancer agents by restoring p53 function.1 Herein the synthesized phthalazino[1,2-b]quinazolinones were discovered as p53 activators in bladder cancer cells. 10-Bromo-5-(2-dimethylamino-ethylamino)phthalazino[1,2-b]quinazolin-8-one (5da) was identified as the most promising candidate in view of both its anticancer activity and mechanisms of action. 5da exhibited strong anticancer activity on a broad range of cancer cell lines and significantly reduced tumor growth in xenograft models at doses as low as 6 mg/kg. Furthermore, 5da caused cell cycle arrest at S/G2 phase, induced apoptosis, changed cell size, and led to cell death by increasing the proportion of sub-G1 cells. Molecular mechanism studies suggested that accumulation of phospho-p53 in mitochondria after 5da treatment resulted in conformational activation of Bak, thereby evoking cell apoptosis, finally leading to irreversible cancer cell inhibition. Our present studies furnish new insights into the molecular interactions and anticancer mechanisms of phospho-p53-dependent quinazolinone compound.
- Zhang, Guo-Hai,Yuan, Jing-Mei,Qian, Gang,Gu, Chen-Xi,Wei, Kai,Mo, Dong-Liang,Qin, Jiang-Ke,Peng, Yan,Zhou, Zu-Ping,Pan, Cheng-Xue,Su, Gui-Fa
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p. 6853 - 6866
(2017/09/07)
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- Azolylthioacetamides as a potent scaffold for the development of metallo-β-lactamase inhibitors
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In an effort to develop new inhibitors of metallo-β-lactamases (MβLs), twenty-eight azolylthioacetamides were synthesized and assayed against MβLs. The obtained benzimidazolyl and benzioxazolyl substituted 1–19 specifically inhibited the enzyme ImiS, and 10 was found to be the most potent inhibitor of ImiS with an IC50 value of 15 nM. The nitrobenzimidazolyl substituted 20–28 specifically inhibited NDM-1, with 27 being the most potent inhibitor with an IC50 value of 170 nM. Further studies with 10, 11, and 27 revealed a mixed inhibition mode with competitive and uncompetitive inhibition constants in a similar range as the IC50 values. These inhibitors resulted in a 2–4-fold decrease in imipenem MIC values using E. coli cells producing ImiS or NDM-1. While the source of uncompetitive (possibly allosteric) inhibition remains unclear, docking studies indicate that 10 and 11 may interact orthosterically with Zn2 in the active site of CphA, while 27 could bridge the two Zn(II) ions in the active site of NDM-1 via its nitro group.
- Xiang, Yang,Chang, Ya-Nan,Ge, Ying,Kang, Joon S.,Zhang, Yi-Lin,Liu, Xiao-Long,Oelschlaeger, Peter,Yang, Ke-Wu
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supporting information
p. 5225 - 5229
(2017/11/13)
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- Triazolylthioacetamide: A Valid Scaffold for the Development of New Delhi Metallo-β-Lactmase-1 (NDM-1) Inhibitors
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The metallo-β-lactamases (MβLs) cleave the β-lactam ring of β-lactam antibiotics, conferring resistance against these drugs to bacteria. Twenty-four triazolylthioacetamides were prepared and evaluated as inhibitors of representatives of the three subclasses of MβLs. All these compounds exhibited specific inhibitory activity against NDM-1 with an IC50 value range of 0.15-1.90 μM, but no activity against CcrA, ImiS, and L1 at inhibitor concentrations of up to 10 μM. Compounds 4d and 6c are partially mixed inhibitors with Ki values of 0.49 and 0.63 μM using cefazolin as the substrate. Structure-activity relationship studies reveal that replacement of hydrogen on the aromatic ring by chlorine, heteroatoms, or alkyl groups can affect bioactivity, while leaving the aromatic ring of the triazolylthiols unmodified maintains the inhibitory potency. Docking studies reveal that the typical potent inhibitors of NDM-1, 4d and 6c, form stable interactions in the active site of NDM-1, with the triazole bridging Zn1 and Zn2, and the amide interacting with Lys 211 (Lys224).
- Zhai, Le,Zhang, Yi-Lin,Kang, Joon S.,Oelschlaeger, Peter,Xiao, Lin,Nie, Sha-Sha,Yang, Ke-Wu
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supporting information
p. 413 - 417
(2016/05/19)
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- Antiurease, antiphosphodiesterase and antiglycation studies of Pd(II) complexes with monodentate hydrazides
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The present study was aimed to synthesize and characterize a series of Pd(II)-benzohydrazide complexes with subsequent high throughput screening to seek their effects as enzyme inhibitors and antiglycating agents. Based on complete characterization via elemental (CHN, Pd) analysis, physical (conductivity, magnetic moment) measurements and spectral (FT-IR, 1H-NMR, 13C-NMR) techniques, all Pd(II) complexes were identified as diamagnetic, neutral and orienting in trans square planar geometry with general formula [PdL2Cl2]. The benzohydrazide (L) in these complexes depicts monodentate behavior, providing terminal amino nitrogen as a donor atom. Compared to inactive precursors (free benzohydrazides and Pd2+), almost all Pd(II) complexes showed in vitro antiglycation activity, illustrating the potential role of resulting complexes in the suppression of diabetes and related disorders. The presence of free carbonyl group in complexes has been recognized as possible cause of antiglycation. This study also indicated Pd(II) compounds as far more superior inhibitors of urease and phosphodiesterase-I than parent ligands; many of them exhibited inhibitions equivalent or even greater than the standard inhibitors (thiourea, urease; EDTA, phosphodiesterase), which shows their potential use in future in the control of peptic ulcer and arthritis, respectively. The structure activity relationship (SAR) study demonstrated that complexation, steric hindrance, position of substituents, electron density around metal centre, hydrogen bonding and coordination mode of complexed ligands play prime role in modulating the biological activities of complexes.
- Qurrat-Ul-Ain,Rasheed, Saima,Mahroof-Tahir, Mohammad,Ashiq, Uzma,Jamal, Rifat Ara,Khurshid, Sumaira,Mustafa, Sana
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p. 864 - 881
(2016/11/21)
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- Synthetic studies and antibacterial activity of nucleobases and their N- and S-glucosides from 2-amino benzoic acid and its benzamido derivatives
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A series of S-glucosides 11a-14a and their benzamido derivatives 11b-14b have been synthesized by reacting D-glucose with thiol groups of 5-(2′-aminophenylene)-1,3,4-oxadiazole-2-thioles 7(a,b), 5-(2′-aminophenylene)-1,3,4-thiadiazole-2-thiols 8(a,b), 5-(2′-aminophenylene)-1,2,4-triazole-3-thiols 9(a,b) and 5-(2′-aminophenylene)-4-N-amino-1,2,4-triazole-3-thiols 10(a,b). The thiols 7(a,b)-10(a,b) have been synthesized from hydrazides 3(a,b) which already been synthesized from 2-aminobenzoic acid and its benzamido derivative. All synthesized compounds were characterized by IR, UV,1H- and13C- NMR. Nucleobases and a representative of S-glycoside were tested in vitro against the following microorganisms: two Gram-positive bacteria Staphylococcus aureus and Bacillus cereusand two Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and they exhibited significant effects. Amykacine was used as positive standard.
- Benhammadi, Samia,Iraten, Salima,Othman, Adil A.
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p. 2567 - 2576
(2016/11/22)
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- Phthalizine [1,2,b] quinazoline-8-ketone compound and preparation method and application in antitumor drugs of phthalizine [1,2,b] quinazoline-8-ketone compound
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The invention discloses a phthalizine [1,2,b] quinazoline-8-ketone compound, which is characterized in that the structural general formula of the compound is shown in the description, and phthalizine [1,2,b] quinazoline-8-ketone derivatives disclosed by the invention have very strong inhibiting effect on common cancer cells such as human gastric carcinoma cells (MGC-803), human lung cancer cells (NCI-H460), human hepatoma cells (HepG-2), cervical carcinoma cells (Hela), human bladder cancer cells (T-24) and the like, can induce apoptosis of the cancer cells, hence the phthalizine [1,2,b] quinazoline-8-ketone and derivatives thereof have potential application in preparation of antitumor drugs.
- -
-
Paragraph 0014; 0043; 0044
(2017/02/24)
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- Preparation and application of benzoyl hydrazine derivative
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The present invention relates to a fluorescent molecular probe, and particularly to preparation and application of a benzoyl hydrazine derivative . The structure of the benzoyl hydrazine derivative P is as shown in a formula 1. A preparation method comprises the following steps: heating ethyl anthranilate and hydrazine hydrate to reflux in anhydrous alcohol for 4-6 h, cooling down the mixture until the temperature reaches the room temperature, then precipitating and filtering a solid, and washing the solid with anhydrous alcohol , and drying to obtain an intermediate compound; and enabling the intermediate to react with 2-hydroxy-1-naphthaldehyde for 4-6 hours in anhydrous alcohol at a temperature of 70-80 DEG C, cooling down the mixture, then precipitating and leaching a solid, then washing the solid, and drying the solid to obtain a yellowish solid pure product P. The benzoyl hydrazine derivative P can be used as a fluorescent probe to implement identification and detection on Mg2+. The benzoyl hydrazine derivative P obtained by an effective synthesis means has relatively good selectivity on Mg2+, and on the basis of optimized experimental conditions, detection on Mg2+ can be implemented. The formula 1 is as shown in the specification.
- -
-
Paragraph 0021; 0022; 0023
(2016/10/08)
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- Synthesis of novel triazoles and a tetrazole of escitalopram as cholinesterase inhibitors
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A novel serie of escitalopram triazoles (60-88) and a tetrazole (89) have been synthesized and subjected to a study to establish the inhibitory potential of these compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some selectivity in inhibition has been observed. The 4-chlorophenyl- (75, IC50, 6.71 ± 0.25 μM) and 2-methylphenyl- (70, IC50, 9.52 ± 0.23 μM) escitalopram triazole derivatives depicted high AChE inhibition, while 2-fluorophenyl- (76, IC50 = 4.52 ± 0.17 μM) and 4-fluorophenyl- (78, IC50 = 5.31 ± 0.43 μM) have found to be excellent BChE inhibitors. It has also been observed that ortho, meta and para substituted electron donating groups increase the inhibition, while electron withdrawing groups reduce the inhibition. Docking analyses of inhibitors with AChE have depicted the binding energies for 70 and 75 as ΔGbind -6.42 and -6.93 kcal/mol, respectively, while ligands 76 and 78 have shown the binding affinity ΔGbind -9.04 and -8.51 kcal/mol, respectively, for BChE.
- Mehr-Un-Nisa,Munawar, Munawar A.,Chattha, Fauzia A.,Kousar, Samina,Munir, Jawaria,Ismail, Tayaba,Ashraf, Muhammad,Khan, Misbahul A.
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p. 6014 - 6024
(2015/11/11)
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- Aldehyde-specific quinazoline ring-closure for highly sensitive fluorescent and redox formaldehyde detection
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Structurally tunable small signaling molecules have been specifically designed to probe-free formaldehyde concentrations as low as 0.1 ppm, establishing the utility of probing the exposure limit for safe human consumption according to the guidelines suggested by W.H.O. The substrate, 2-aminobenzoylhydrazide, fluorescent core skeleton was designed for the construction of diverse quinazoline compounds with combinatorial substituent-pending potentials via rapid condensation reactions with aldehyde groups. After identifying the fluorescent species by 1H NMR and X-ray crystallography, we demonstrate that the fluorescent emission is substituent dependent and that, by simple structural variation, the fluorescence can be tunable through controlling internal charge transfer (ICT) within a dye platform. Finally, by introducing more electron-rich ferrocene into the substrate to further undermine the ICT process, we demonstrate highly sensitive formaldehyde sensing through dual signal output, including fluorescence and redox potential.
- Huang, Wei,Shen, Fuxing,Wu, Dayu
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supporting information
p. 896 - 898
(2015/08/24)
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- Studies on chemistry, spectroscopy and antioxidant activities of chromium(III)-hydrazide complexes
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Acid hydrazides are vital chemical entities due to their biological activities. Upon complexation with certain metal ions, their biological activities are known to be positively enhanced. The present work describes the synthesis of Cr(III)-hydrazide complexes, and their structural, spectroscopic and antioxidant properties to reveal their chemistry and biochemistry. Physical (magnetic moment, conductivity measurements), analytical (C, H, N and Cr analysis) and spectral (EI-Mass, FTIR) techniques are used for the characterization of synthesized compounds. All Cr(III)-hydrazide complexes exhibit octahedral geometry with general formula [Cr(L)2(H2O)2]Cl3. In these complexes, the hydrazide ligands are coordinated via carbonyl oxygen and terminal amino nitrogen in a bidentate fashion. All Cr(III)-hydrazide complexes were screened for in vitro diphenyldipicryl hydrazine (DPPH), superoxide dismutase and nitric oxide radical scavenging activities. Majority of the Cr(III)-hydrazide complexes were found to be more potent scavengers than their uncoordinated hydrazide ligands. This study demonstrates an interesting structure-activity relationship (SAR) which is presented here.
- Shamshad, Bushra,Jamal, Rifat A.,Ashiqa, Uzma,Mahrooof-Tahirb, Mohammad,Shaikha, Zara,Sultana, Sadaf,Khanc, Khalid M.
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p. 798 - 806
(2015/12/01)
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- Synthesis of diverse azolo[c]quinazolines by palladium(II)- catalyzed aerobic oxidative insertion of isocyanides
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We report the palladium(II)-catalyzed aerobic oxidative coupling of isocyanides with various (2-aminophenyl)azoles using air as the stoichiometric oxidant. A diverse range of medicinally valuable azolo[c]quinazolines was obtained by this new approach.
- Vlaar, Tjostil,Bensch, Lisa,Kraakman, Jasper,Vande Velde, Christophe M. L.,Maes, Bert U. W.,Orru, Romano V. A.,Ruijter, Eelco
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supporting information
p. 1205 - 1209
(2014/05/06)
-
- Design, green synthesis, and anti-inflammatory activity of schiff base of 1,3,4-oxadiazole analogues
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Cyclooxygenase enzyme is a validated therapeutic target for designing drug molecules with anti-inflammatory activity. Herein, a series of various schiff base of 1,3,4-oxadiazole analogues were designed. Considering reasonable structural similarity of the target compounds with the commonly used anti-inflammatory drug indomethacin, it was decided to dock the target compounds into the active site of the molecular target of indomethacin. Prior to docking, the active sites of the proteins are identified. The docking study is performed using the UCSF DOCK 6.5 program. And also the utilization of principles involved in green chemistry is significantly reducing chemical waste and reaction times. To illustrate these advantages in the synthesis of bioactive oxadiazole derivatives, various environmentally benign protocols that involve greener alternatives were studied. The efficiency of microwave heating technology has resulted in remarkable reductions of reaction times (reduced from days and hours to minutes and seconds) with better product yield. The structures of newly synthesized compounds have been elucidated on the basis of IR, 1H NMR, 13C NMR, LC-MS and elemental analysis. An evaluation of the anti-inflammatory activity of the prepared compounds has indicated that some of them exhibited moderate to significant activity as compared to indomethacin.
- Sahoo, Biswa Mohan,Dinda, Subas Chandra,Kumar, B.V.V. Ravi,Panda, Jnyanaranjan,Brahmkshatriya, Pathik S.
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- Synthesis of some 1,3,4-thiadiazole derivatives as inhibitors of Entamoeba histolytica
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In the quest for potent anti-amoebic agents, some 1,3,4-thiadiazole derivatives were synthesized and characterized by spectral data. The purity of the compounds was confirmed by elemental analysis. All the compounds were screened in vitro against HM1:IMSS strain of Entamoeba histolytica by microdilution method. The results revealed that compounds 1 (IC50 = 0.670 μM), 3 (IC50 = 1.60 μM) and 8 (IC50 = 0.522 μM) had much better anti-amoebic activity than the reference drug metronidazole (IC50 = 1.80 μM). Further, cytotoxicity of the compounds having IC50 value less than metronidazole was assessed by MTT assay on human breast cancer MCF-7 cell line and all the compounds were found low cytotoxic in the concentration range of 2.5-250 μM. Preliminary results indicate that these three compounds (1, 3 and 8) may be subjected to further investigations and it may be hoped that the present study will stimulate efforts towards the development of novel effective anti-amoebic agents.
- Siddiqui, Shadab Miyan,Salahuddin, Attar,Azam, Amir
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p. 1305 - 1312
(2013/04/10)
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- 2-(Quinolin-4-ylthio)-1,3,4-oxadiazole derivatives: Design, synthesis, antibacterial and antifungal studies
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A series of novel hybrid 2-(7-chloroquinolin-4-ylthio)-5-(substituted)-1,3, 4-oxadiazole derivatives have been designed, synthesized which contains different pharmacophores like quinoline and 1,3,4-oxadiazole linked via sulfur atom. All the newly synthesized derivatives have been characterized by IR, 1H NMR, 13C NMR spectral and elemental analysis. Further, All the final synthesized scaffolds have been subjected to in vitro antimicrobial activity against several bacteria (E.coli, P.aeruginosa, S.aureus, S.pyogenus) and fungi (C.albicans, A.niger, A.clavatus) using broth dilution technique. Among the compounds tested, compounds 3f substituted with coumarin analogue and 3b with amine group at second position of phenyl to oxadiazole moiety are found to be most potent.
- Modh, Rahul P,Shah, Dhruvin,Chikhalia, Kishor H
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p. 1318 - 1324
(2014/01/06)
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- Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents
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A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56-3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study.
- Du, Qian-Ru,Li, Dong-Dong,Pi, Ya-Zhou,Li, Jing-Ran,Sun, Jian,Fang, Fei,Zhong, Wei-Qing,Gong, Hai-Bin,Zhu, Hai-Liang
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p. 2286 - 2297
(2013/05/09)
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- Characterization of a highly Cu2+-selective fluorescent probe derived from rhodamine B
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A rhodamine B derivative was synthesized and characterized as a highly selective and sensitive probe for Cu2+ in ethanol-water solution (2:3, v:v, pH7.4, 50 mM HEPES). A prominent fluorescence enhancement at 575 nm was observed in the presence of Cu2+, accompanied by the change in the absorption spectrum. Under the optimal conditions, a good linear range of 0.5-1.5 μM with a detection limit of 1.6 × 10-7 M were obtained. Furthermore, confocal laser scanning microscopy experiments have proven that this probe is cell-permeable and can respond to changes in intracellular Cu2+ in living cells.
- Yu, Chunwei,Wang, Ting,Xu, Ke,Zhao, Jing,Li, Maohua,Weng, Shixing,Zhang, Jun
-
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- Synthesis, molecular modeling and biological evaluation of 2-(benzylthio)-5-aryloxadiazole derivatives as anti-tumor agents
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A series of 2-(benzylthio)-5-aryloxadiazole derivatives have been designed and synthesized, and their biological activities are also evaluated for EGFR inhibitory activity. Fourteen compounds among the twenty compounds are reported for the first time. Their chemical structures are characterized by 1H NMR, MS, and elemental analysis. Anti-proliferative and EGFR inhibition assay results have demonstrated that compound 3e shows the most potent biological activity (IC50 = 1.09 μM for MCF-7 and IC50 = 1.51 μM for EGFR). Docking simulation has been performed to position compound 3e into the EGFR active site to determine the probable binding model, with an estimated binding free energy value of -10.7 kcal/mol. Compound 3e with potent inhibitory activity in tumor growth inhibition may be a promising anti-tumor leading compound for the further research.
- Liu, Kai,Lu, Xiang,Zhang, Hong-Jia,Sun, Juan,Zhu, Hai-Liang
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experimental part
p. 473 - 478
(2012/03/13)
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- Comparison between antioxidant activity of 2,5-disubstituted 1,3,4-oxadiazoles containing heteroaromatic ring and aromatic ring at 2nd position
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A series of 4-[5-(substitutedphenyl)-1,3,4-oxadiazol- 2-yl]-pyridine) and 2-[5-substitutedphenyl)-1,3,4- oxadiazol-2-yl]-benzenamine derivatives were synthesized from substituted esters and hydrazine hydrate in the presence of ethanol to give isonicotinic acid hydrazide and 2-aminobenzohydrazide followed by reaction with phosphorus oxychloride and various aromatic acids. All the compounds were tested for their in vitro antioxidant activity by 1,1-diphenyl-2-picryl hydrazyl (DPPH) method. Compounds containing aromatic group at 2nd position showed significant activity as compared to standard (ascorbic acid) which concludes that the presence of aromatic group increases the free radical scavenging activity. Springer Science+Business Media, LLC 2010.
- Maheshwari, Radhika,Chawla, Pooja,Saraf, Shubhini A.
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experimental part
p. 1650 - 1655
(2012/06/15)
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- Synthesis, X-Ray crystal structure and spectroscopic properties of 1,2,3,4-tetrahydro-2-(thenyl)-3-(N-thenylidine)-4-oxoquinazoline
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The Schiff base formed between anthraniloyl hydrazide and thiophen-2-aldehyde is synthesized. Reaction of this Schiff base with VOSO 4 in methanol at room temperature does not yield the expected vanadium complex; instead, the Schiff base is transformed to 1,2,3,4-tetrahydro-2-(thenyl)-3-(N-thenylidine)-4-oxoquinazoline, which has been characterized by elemental analyses and by LC-MS, i.r., n.m.r. and electronic spectroscopies. The X-ray crystal structure of the quinazoline product is reported. The compound crystallizes with monoclinic (P21/n) space group, and the cell parameters are: a = 5.9442(7) A, b = 13.6357(15) A, c = 19.455(2) A, β = 90.499(2)°. The oxo-quinazoline product is found to be luminescent when excited at its lowest energy transition.
- Naskar, Sumita,Naskar, Subhendu,Blake, Alexander J.,Tadesse, Haregewine,Chattopadhyay, Shyamal Kumar
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experimental part
p. 986 - 990
(2012/01/13)
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- Identification of novel quinazolin-4(3H)-ones as inhibitors of thermolysin, the prototype of the M4 family of proteinases
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A combinatorial series of novel quinazolin-4(3H)-ones were synthesised and their structures were established based on spectroscopic data (IR, NMR, EI-MS, and FAB-MS). The compounds were tested for inhibition of the zinc metalloproteinase thermolysin (TLN) utilizing a chemical array-based approach. Some of the compounds were found to inhibit TLN, with IC50 values ranging from 0.0115 μM (compound 3) to 122,637 μM (compound 29). Compound 3 [3-phenyl-2-(trifluoromethyl) quinazolin-4(3H)-one] (IC50 = 0.0115 μM) and compound 35 [3-(isopropylideneamino)-2,2-dimethyl-2,3-dihydroquinazolin-4 (1H)-one] (IC50 = 0.2477 μM) were found to be the most potent inhibitors.
- Khan, Mahmud Tareq Hassan,Khan, Rasool,Wuxiuer, Yimingjiang,Arfan, Mohammad,Ahmed, Manzoor,Sylte, Ingebrigt
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scheme or table
p. 4317 - 4327
(2010/09/12)
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- Synthesis and evaluation of adenosine antagonist activity of a series of [1,2,4]triazolo[1,5-c]quinazolines
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A series of [1,2,4]triazolo[1,5-c]quinazolines were prepared in satisfactory yields by reaction of some derivatives of 2-aminobenzohydrazide with several hydrochlorides of aromatic amidines, and their binding affinities for the recombinant human adenosine A2A and A2B receptors were determined. None of the new compounds showed noteworthy affinity for these receptors, though a very high affinity for the A2A receptor and, consequently, a high level of A2A/A2B selectivity was revealed for one of the synthesized compounds.
- Balo, Carmen,Lopez, Carmen,Brea, Jose Manuel,Fernandez, Franco,Caamano, Olga
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p. 372 - 375
(2008/02/02)
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- A diversity oriented synthesis of 2,10-dioxo-10H-1,2,3,4,4a,5-hexahydropyridazino[3,2-b]quinazolines
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A parallel method for the synthesis of the title compounds is described. Thus, methyl anthranilates (5) are transformed into 2-aminobenzohydrazides (3) which were treated with 4-oxo acids (4) to afford in high yields and acceptable purity of piridazino[3,2-b]quinazolines (1). Compounds (1) present four diversity centers (R1, R2, R3, and R4). The range of chemically acceptable substituents at each center has been evaluated. The isolation of a possible intermediate in the formation of 1, which presents an amino structure (10), has allowed proposing a complete mechanistic rationalization for the formation of structures (1).
- Schuler, Elisabeth,Juanico, Nacho,Teixidó, Jordi,Michelotti, Enrique L.,Borrell, José I.
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p. 161 - 173
(2007/10/03)
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- Metal complexes and solvent extraction properties of isonitrosoacetophenone 2-aminobenzoylhydrazone
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Three types of copper complexes as well as an oximate-bridged nickel complex with isonitrosoacetophenone 2-aminobenzoylhydrazone (H2L) have been prepared in ethanolic solution and characterized by elemental analyses, IR, 1H NMR, UV-vis and magnetic susceptibility measurement. IR spectra show the ligand coordinates as a neutral, monoanionic and dianionic O,N,N-tridentate acylhydrazoneoxime ligand depending reaction conditions and metal salts employed. The elemental analyses results, spectroscopic and magnetic data are consistent with the formation of mononuclear copper complexes and binuclear complexes with both copper and nickel. The effects of varying pH and solvent on the absorption behavior of both ligand and complexes have been investigated. The extraction ability of acylhydrazoneoxime ligand has been examined by the liquid-liquid extraction of selected transition metal [Cu2+, Ni2+, Co2+, Cr3+, Hg2+, Zn2+, Cd2+ and Mn2+] cations. The ligand shows strong binding ability toward copper(II) ion.
- Gup, Ramazan,Giziroglu, Emrah
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p. 719 - 726
(2007/10/03)
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- Synthesis and Pharmacological Evaluation of Fenamate Analogues: 1,3,4-Oxadiazol-2-ones and 1,3,4-Oxadiazole-2-thiones
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A series of fenamate pyridyl or quinolinyl analogues of 1,3,4-oxadiazol-2-ones 5a-d and 6a-r, and 1,3,4-oxadiazole-2-thiones 5e-g and 6s-v, respectively, have been synthesized and evaluated for their analgesic (hot-plate), antiinflammatory (carrageenin induced rat's paw edema) and ulcerogenic effects as well as plasma prostaglandin E2 (PGE 2) level. The highest analgesic activity was achieved with compound 5a (0.5, 0.6, 0.7 mmol/kg b.wt.) in respect with mefenamic acid (0.4 mmol/kg b.wt.). Compounds 6h, 61 and 5g showed 93, 88 and 84% inhibition, respectively on the carrageenan-induced rat's paw edema at dose level of 0.1mmol/kg, b.wt, compared with 58% inhibition of mefenamic acid (0.2mmol/kg b.wt.). Moreover, the highest inhibitory activity on plasma PGE2 level was displayed also with 6h, 61 and 5g (71, 70, 68.5% respectively, 0.1mmol/kg b.wt.) compared with indomethacin (60%, 0.01 mmol/kg b.wt.) as a reference drug. In addition 6i, 6k, 6p, 6r, 6t and 6v were devoid of any ulcerogenicity.
- El-Azzounyl, Aida A.,Maklad, Yousreya A.,Bartsch, Herbert,Zaghary, Wafaa A.,Ibrahim, Waleed M.,Mohamed, Mosaad S.
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p. 331 - 356
(2007/10/03)
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- New derivatives of 3-amino-2(1H)-thioxo-4(3H)-quinazolinone. Part II *. Reaction of 3-amino-2(1H)-thioxo-4(3H)-quinazolinone with cyanogen bromide
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3-Amino-2(1H)-thioxo-4(3H)-quinazolinone was subjected to reactions with bromocyane under different experimental conditions and the following products were obtained: 2,2′-thiodi-[3-amino-4(3H)-quinazolinone], 2-amino-5-oxo-1,3,4-thiadiazol-[2,3-b]quinazoline and 1,2-bis[3-thioxo-4(3H)-oxo-quinazoline]guanidine. 2-Amino-5-oxo-1,3,4-thiadiazol[2,3-b]quinazoline was condensed with selected α,β-unsaturated aldehydes: crotonic and cinnamic to yield 3-methyl-3(5-oxo-1,3,4-thiadiazol-[2,3-b]-quinazolin-2-ylamino)-propanal-1 and 2-cinnamylidenoamino-5-oxo-1,3,4-thiadiazol-[2,3-b]-quinazoline.
- Nawrocka,Stasko
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p. 792 - 796
(2007/10/03)
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- Pentafluorophenyl ester activation for the preparation of N,N'-diaroylhydrazines
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Procedures are reported for the preparation of N,N'-diaroylhydrazines using pentafluorophenyl (Pfp) ester activation of aryl carboxylic acids. Mild conditions which avoid intermediate protection of ring substituents, allows the synthesis of both symmetrical and unsymmetrical diaroylhydrazines in high yields. The recent discovery of potent HIV-1 integrase inhibition by N,N'-bis-salicylhydrazine (1) highlights the potential importance of this class of compounds. The stability of pre-activated Pfp ester intermediates and the facility with which N,N'-diaroylhydrazines can be synthesized using this procedure (stirring at room temperature in DMF) may make the method particularly attractive for synthesis of hydrazide libraries.
- Zhao, He,Burke Jr., Terrence R.
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p. 4219 - 4230
(2007/10/03)
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- Aziridination of alkenes using 3-acetoxyamino-2-trifluoromethylquinazolin-4(3H)-one
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Oxidation of 3-amino-2-trifluoromethylquinazolin-4(3H)-one 6 with lead tetraacetate in dichloromethane gives the title 3-acetoxyamino derivative 7 which is isolable at room temperature and considerably more stable than the corresponding 2-alkyl substituted analogues. Compound 7 aziridinates alkenes in yields which are consistently higher than those from the 2-alkyl substituted analogues. Aziridinations using 3-acetoxyaminoquinazolinones bearing other electron-withdrawing groups on the 2-position of the quinazolinone ring have been examined.
- Atkinson, Robert S.,Coogan, Michael P.,Cornell, Clive L.
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p. 157 - 166
(2007/10/03)
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