- A discrete dysprosium trigonal prism showing single-molecule magnet behaviour
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A magnetic personality: A unique dysprosium trigonal prism with a new polydentate Schiff-base ligand behaves as a single molecule magnet (SMM), which may stimulate further investigations into the relaxation dynamics of SMMs with different topologies (see
- Tian, Haiquan,Wang, Min,Zhao, Lang,Guo, Yun-Nan,Guo, Yang,Tang, Jinkui,Liu, Zhiliang
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- Exchange Interactions Switch Tunneling: A Comparative Experimental and Theoretical Study on Relaxation Dynamics by Targeted Metal Ion Replacement
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The magnetic relaxation and magnetization blocking barriers of tailor-made homo- and heterodinuclear compounds [Dy2(opch)2(OAc)2(H2O)2]?MeOH (1) and [DyMn(opch)2(OAc)(MeOH)(H2O)
- Tian, Haiquan,Ungur, Liviu,Zhao, Lang,Ding, Shuai,Tang, Jinkui,Chibotaru, Liviu F.
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- A chromone based Schiff base: An efficient colorimetric sensor for specific detection of Cu (II) ion in real water samples
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A new chromone based Schiff base ligand L was synthesized by the condensation of 3-formyl chromone and pyrazine-2-carbohydrazide as a colorimetric probe to detect Cu (II) ions selectively. An instant visual colour change from colourless to yellow was obtained on addition of Cu2+ ions to the probe L solution, while other metal ions found ineffective. The ligand L was characterized by 1H NMR, FTIR and HRMS spectral techniques. UV-Visible spectroscopic technique was used to study the sensing ability of probe L for copper ions above other metal ions. The Job's plot obtained from absorption studies and HRMS data confirmed that the Cu2+ ions bind with ligand L in 1:1 stoichiometric ratio. DFT computations were also supported the binding framework between L and Cu (II) ions. The LOD value and the association constant were obtained 3.9 × 10?7 M and 2.3 × 105 M?1 respectively, via Benesi-Hildebrand equation. Selectivity of L towards Cu2+ ions was also studied and it was found that the probe L worked specifically for copper ions without any considerable influence of other intruding metal ions. In addition, in real water samples, the ligand L was fully implemented for identification and quantification of Cu2+ ions.
- Tomer, Nisha,Goel, Apurva,Ghule, Vikas D.,Malhotra, Rajesh
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- Pyrazinederived 1,2,3-triazole linked silanes and their magnetic nanoparticles for the colorimetric and fluorimetric dual sensing of Cu2+ ions
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In this article, pyrazinebased 1,2,3-triazole linked organosilanes have been synthesized and characterized with techniques like 1H, 13C NMR spectroscopy and mass spectrometry. The synthesized compound 6b (PTSR)could selectively and sensitively recognize Cu2+ ionswhereas the interference from other metal ions was negligible. The 6(b) behaves as reversible sensor for Cu2+ions. The fluorescence response of 6(b) toward Cu2+ions showed a significant fluorescence quenching. Further,the sensing application was enhanced by the immobilization of organic moiety on the magnetic silicasurface. The adsorption of organosilaneis confirmed by various techniques such as FT-IR, EDX, XRD, TGA, SEM, HR-TEM, DLS. The hybrid magnetic nanoparticles (HNPs)are found to be more sensitive for Cu2+ ions with low LOD as compare to 6(b)i.e. 2.7 × 10?6 M. In addition, the synthesized alkynes and silanes were examined fordrug-likeness profile by using online available toolkits like MOLINSPIRATION and ADMET.
- Devi, Anita,Diksha,Kaur, Jashandeep,Mohit,Priyanka,Saini, Anamika,Singh, Gurjaspreet,Suman,Sushma
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- 1H-1,2,3-triazole embedded Isatin-Benzaldehyde-bis(heteronuclearhydrazones): design, synthesis, antimycobacterial, and cytotoxic evaluation
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Rapid growth of global drug-resistant tuberculosis and urgent requirement for short treatment regimens is stimulating the need for discovery of new TB drugs. In this work, we report the design, synthesis and in vitro antimycobacterial evaluation of a library of isatin-derived bis(heteronuclear hydrazones). Evaluation results revealed that the inclusion of isoniazid core into 1H-1,2,3-triazole tethered isatin-benzaldehydes improved the antimycobacterial activity on tuberculosis mc26230 strain and significantly reduced the cytotoxicity against Vero cells. However, the introduction of semicarbazones/thiosemicarbazones or pyrazine-2-carbohydrazide produced the opposite effects. The compounds with isoniazid and polar-donating groups at the C-5 position of isatin emerged as the most promising conjugates with MIC99?=?0.36?μg/ml. The most active compounds were non-cytotoxic to Vero cells (IC50>100?μg/ml) with selectivity indices >277.
- Sharma, Bharvi,Kumar, Sumit,Preeti,Johansen, Matt D.,Kremer, Laurent,Kumar, Vipan
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p. 301 - 307
(2021/12/09)
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- New silver(I) phosphino complexes: Evaluation of their potential as prospective agents against Mycobacterium tuberculosis
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Despite being a preventable and curable disease, Tuberculosis (TB) is the world's top infectious killer. Development of new drugs is urgently needed. In this work, the synthesis and characterization of new silver(I) complexes, that include N′-[(E)-(pyridine-2-ylmethylene)pyrazine-2-carbohydrazide, HPCPH, as main ligand and substituted aryl-phosphines as auxiliary ligands, is reported. HPCPH was synthesized from pyrazinoic acid, the active metabolite of the first-line antimycobacterial drug pyrazinamide. Complexes [Ag(HPCPH)(PPh3)2]OTf (1), [Ag(HPCPH)((P(p-tolyl)3)2]OTf (2) and [Ag(HPCPH)(P(p-anisyl)3)2]OTf (3) were characterized in solid state and in solution by elemental analysis and FTIR and NMR spectroscopies (OTf[dbnd]triflate). Crystal structures of (1,2) were determined by XRD. The Ag atom is coordinated to azomethine and pyridine nitrogen atoms of HPCPH ligand and to the phosphorous atom of each aryl-phosphine co-ligand. Although HPCPH did not show activity, the Ag(I) compounds demonstrated activity against Mycobacterium tuberculosis (MTB), H37Rv strain, and multi-drug resistant clinical isolates (MDR-TB). Globally, results showed that the compounds are not only effective against the sensitive strain, but are more potent against MDR-TB than antimycobacterial drugs used in therapy. The compounds showed low to moderate selectivity index values (SI) towards the bacteria, using MRC-5 cells (ATCC CCL-171) as mammalian cell model. Interaction with DNA was explored to get insight into the potential mechanism of action against the pathogen. No significant interaction was detected, allowing to discard this biomolecule as a potential molecular target. Compound 1 was identified as a hit compound (MIC90 2.23 μM; SI 4.4) to develop further chemical modifications in the search for new drugs.
- Maldonado, Yndira Dolores,Scalese, Gonzalo,Manieri, Karyn Fernanda,Pavan, Fernando R.,Aguirre Méndez, Larry D.,Gambino, Dinorah
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- A chromone hydrazide Schiff base fluorescence probe with high selectivity and sensitivity for the detection and discrimination of human serum albumin (HSA) and bovine serum albumin (BSA)
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The discrimination and identification of human serum albumin (HSA) and bovine serum albumin (BSA) is very important, which is due to the vital roles of two SAs in biological and pharmaceutical research. Based on structural screening and docking calculation from a series of homologues, a coumarin Schiff base fluorescent probe 3-hydroxy-N′-((4-oxo-4H-chromen-3-yl)methylene)-2-naphthohydrazide (HCNH) has been designed and synthesized, which could effectively discriminate HSA and BSA. The probe HCNH exhibited superior sensitivity toward HSA and BSA with the detection limits of 10.62 nM and 16.03 nM in PBS solution, respectively. The binding mechanism of HCNH with SAs was studied by Job's plot analysis, SA destruction and displacement assay. Molecular docking and DFT methods were utilized to provide deep insight into the spatial conformation change of HCNH and binding sites in HSA/BSA. The conformation of HCNH was significantly influenced by the microenvironment provided by HSA and BSA, therefore its fluorescence emission was affected correspondingly. Non-toxic probe HCNH could be successfully used for fluorescence bio-imaging of HSA in cancer cells, which is significantly different from normal cells and favors the application in medical diagnosis.
- Yan, Xiao-Jing,Li, Zhe,Liu, Hai-Bo,Wang, Zhi-Gang,Fan, Jing,Xie, Cheng-Zhi,Li, Qing-Zhong,Xu, Jing-Yuan
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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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- Evaluation and Docking Study of Pyrazine Containing 1, 3, 4-Oxadiazoles Clubbed with Substituted Azetidin-2-one: A New Class of Potential Antimicrobial and Antitubercular
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Background Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the main killers of people all over the world. The major hurdles with existing therapy are the lengthy regimen and appearance of multi drug resistant (MDR) and extensively drug resistant (XDR) strains of M.tuberculosis. Aims The present work was aimed to synthesize and determine antitubercular and antimicrobial potential of some novel 3-chloro-4-aryl-1-[4-(5-pyrazin-2-yl[1,3,4]oxadiazole-2-ylmethoxy)-phenyl]-azetidin-2-one derivatives 7 (a - h) from pyrazinoic acid as precursor, which is a well-established antitubercular agent. Here we report the synthesis of a new class of heterocyclic molecules in which pyrazine, 1, 3, 4-oxadiazole and azetidinone moieties were present in one frame work. Methods Pyrazinoic acid (1) was esterified first (2) followed by amination to produce hydrazide (3) which was refluxed with POCl3 to obtain 2-chloromethyl-5pyrazino-1, 3, 4-oxadiazole (4). This was then further reacted with 4-amino phenol to obtain 4-[5-pyrazino-1, 3, 4-oxadiazol-2-yl-methoxy]-phenyl amine (5) which on condensation with various aromatic aldehydes afforded a series Schiff's bases 6(a-h). Dehydrative annulations of 6(a-h) in the presence of chloroacetyl chloride and triethylamine yielded 3-chloro-4-aryl-1-[4-(5-pyrazin-2-yl-[1, 3, 4]oxadiazole-2-ylmethoxy)-phenyl]-azetidin-2-one derivatives 7(a-h). Antibacterial, antifungal and antitubercular potential of all the synthesized compounds were assessed. Docking study was performed using the software VLife Engine tools of Vlifemds 4.6 on the protein lumazine synthase of M. tuberculosis (PDB entry code 2C92). Results The present studies demonstrated that synthesized oxadiazole derivatives have good antimicrobial activity against the various microorganisms. Among the synthesized derivative, 7b and 7g were found to be prominent compounds which have potential antibacterial, antifungal and antitubercular activity (with MIC 3.12 μg/ml and high dock score ranging from -59.0 to -54.0) against Mycobacterium tuberculosis. Conclusions Derivatives 7b and 7g would be effective lead candidates for tuberculosis therapy.
- Das, Rina,Mehta, Dinesh Kumar
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- PIEZO1 AGONISTS FOR THE PROMOTION OF BONE FORMATION
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Disclosed herein are Piezo 1 agonists. Also disclosed herein are methods of stimulating tissue anabolism in a subject comprising administering an effective amount of a Piezo 1 agonist and methods for chemically mimicking mechanical stimulation of a cell expressing Piezo 1 comprising contacting a cell expressing Piezo1 with an effective amount of a Piezo 1 agonist.
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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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- N-acylhydrazones confer inhibitory efficacy against New Delhi metallo-β-lactamase-1
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The expression of β-lactamases, especially metallo-β-lactamases (MβLs) in bacteria is one of the main causes of drug resistance. In this work, an effective N-acylhydrazone scaffold as MβL inhibitor was constructed and characterized. The biological activity assays indicated that the synthesized N-acylhydrazones 1–11 preferentially inhibited MβL NDM-1, and 1 was found to be the most effective inhibitor with an IC50 of 1.2 μM. Analysis of IC50 data revealed a structure–activity relationship, which is that the pyridine and hydroxylbenzene substituents at 2-position improved inhibition of the compounds on NDM-1. ITC and enzyme kinetics assays suggested that it reversibly and competitively inhibited NDM-1 (Ki = 0.29 ± 0.05 μM). The synthesized N-acylhydrazones showed synergistic antibacterial activities with meropenem, reduced 4–16-fold MIC of meropenem on NDM-1- producing E. coli BL21 (DE3), while 1 restored 4-fold activity of meropenem on K. pneumonia expressing NDM-1 (NDM-K. pneumoniae). The mice experiments suggested that 1 combined meropenem to fight against NDM-K. pneumoniae infection in the spleen and liver. Cytotoxicity assays showed that 1 and 2 have low cytotoxicity. This study offered a new framework for the development of NDM-1 inhibitors.
- Gao, Han,Li, Jia-Qi,Kang, Peng-Wei,Chigan, Jia-Zhu,Wang, Huan,Liu, Lu,Xu, Yin-Sui,Zhai, Le,Yang, Ke-Wu
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- A quasilinear hydrazone-based mononuclear dysprosium compound with: C 4vsymmetry exhibiting field-induced complex magnetic relaxation
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This paper reports a quasilinear hydrazone-based mononuclear dysprosium(iii) compound, namely, {Dy(Hppyh)2(SCN)3}·2MeOH (I), where Hppyh is pyrazine-2-carboxylic acid pyridin-2-ylmethylene-hydrazide. Compound I behaves as a single-ion magnet (SIM) based on the optimal dc field application of 0.7 kOe, showing a complex magnetic relaxation phenomenon with a tunneling relaxation time of 6.1 ± 0.3 × 10-3 s and an effective spin reversal barrier of 22.6 ± 1.1 K for the low- and high-frequency regions, respectively. More importantly, detailed comparative experimental and theoretical investigations reveal that the complex magnetic relaxation was most likely associated with the single DyIII ion behavior as well as the short-range intermolecular magnetic dipolar interactions.
- Chen, Peiqiong,Guo, Xuefeng,Liu, Dan,Liu, Hou-Ting,Lu, Jing,Sun, Xiao,Tian, Haiquan
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p. 21708 - 21715
(2021/12/13)
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- Novel pyrazine based anti-tubercular agents: Design, synthesis, biological evaluation and in silico studies
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TB continues to be a leading health threat despite the availability of powerful anti-TB drugs. We report herein the design and synthesis of various hybrid molecules comprising pyrazine scaffold and various formerly identified anti-mycobacterial moieties. Thirty-one compounds were screened in vitro for their activity against Mycobacterium tuberculosis H37Rv strain using MABA assay. The results revealed that six compounds (8a, 8b, 8c, 8d, 14b and 18) displayed significant activity against Mtb with MIC values ≤6.25 μg/ml versus 6.25 μg/ml for pyrazinamide. The most active compounds were then assessed for their in vitro cytotoxicity against PBMC normal cell line using MTT assay and showed SI > 200. Several in silico studies have been carried out for target fishing of the novel compounds such as shape-based similarity, pharmacophore mapping and inverse docking. Based on this multi-step target fishing study, we suggest that pantothenate synthetase could be the possible target responsible for the action of these compounds. The most active compounds were then successfully docked into the active site of pantothenate synthetase enzyme with favorable binding interactions. In addition, in silico prediction of physicochemical, ADMET and drug-like properties were also determined indicating that compounds 8b, 8c and 8d are promising candidates for the development of new anti-TB agents with enhanced activity and better safety profile.
- Abdel-Aziz, Marwa M.,Abdel-Ghany, Yasser S.,El-Hawash, Soad A.,Elzahhar, Perihan A.,Hassan, Nayera W.,Ismail, Azza,Nassra, Rasha,Saudi, Manal N.,Sriram, Dharmarajan
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- Design, synthesis and antitrypanosomal activity of heteroaryl-based 1,2,4-triazole and 1,3,4-oxadiazole derivatives
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Two series of novel 1,2,4-triazol-3-yl-thioacetamide 3a-b and 4a-b and 5-pyrazin-2-yl-3H-[1,3,4]oxadiazole-2-thiones 9a-h were designed and synthesized. The compounds prepared have been identified using 1H NMR, 13C NMR and elemental analyses. The synthesized compounds 3a, 3b, 4a, 4b, 9a, 9b, 9d-e and 9f have been evaluated with α-difluoromethylornithine (DFMO) as a control drug for their in vitro antitrypanosomal activity against Trypanosoma brucei. Results showed that 3b was the most active compound in general and also more potent than control DFMO. 3b was 8 folds more potent than the reference with IC50 of 0.79 μM and IC90 of 1.35 μM, respectively compared to DFMO (IC50 = 6.10 μM and IC90 of 8.66 μM). The tested compounds showed moderate cytotoxicity with selectivity indices ranging from 12 (9d) to 102 (3b) against L6 cells. Docking study was performed into ten of T. brucei enzymes which have been identified as potential/valid targets for most of the antitrypanosomal agents. The results of the docking study revealed high binding scores toward many of the selected enzymes. A good correlation was observed only between log (IC50) of antitrypanosomal activity of the new compounds and their calculated Ki values against TryR enzyme (R2 = 0.726). Compound 3b, the most active as antitrypanosomal agents exhibited similar binding orientation and interaction to those of WP6 against TryR enzyme. However, in a next round of work, a complementary studies will be carried out to clarify the mechanism of action of these compounds.
- Abdel-Aziz, Mohamed,Gouda, Ahmed M.,Marzouk, Adel A.,Radwan, Mohamed M.,Shaykoon, Montaser Sh.,Soltan, Osama M.,Wanas, Amira S.,Youssif, Bahaa G. M.
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- A novel hydrazide Schiff base self-assembled nanoprobe for selective detection of human serum albumin and its applications in renal disease surveillance
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Human serum albumin (HSA) is considered as a biomarker for the early diagnosis of renal disease, therefore identifying and detecting HSA in biological fluids (especially urine) with an easy method is of great importance. Herein, we report a novel hydrazide Schiff base fluorescent probe N′-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)pyrazine-2-carbohydrazide (NPC), which self-assembled into nanoparticles in aqueous solution. Based on disassembly-induced emission and the site-specific recognition mechanism, the binding of NPC with HSA resulted in a fluorescence "turn-on"response. Probe NPC exhibited superior selectivity and sensitivity toward HSA with a detection limit of 0.59 mg L-1 in PBS and 0.56 mg L-1 in the urine sample. The site-binding mechanism of NPC with HSA was explored by fluorescence quenching study, Job's plot analysis, HSA destruction, site marker displacement and molecular docking. Fluorescence imaging of HSA in MCF-7 cells was achieved by using a non-toxic NPC probe, suggesting that NPC could be applied to visualize the level of HSA in vivo. More importantly, further practical applications of probe NPC in human urine samples were achieved with satisfactory results by using a fluorometer or test paper, which could provide extensive application in clinical diagnosis.
- Li, Qing-Zhong,Liu, Hai-Bo,Liu, Wei,Wang, Zhi-Gang,Xie, Cheng-Zhi,Xu, Jing-Yuan,Yan, Xiao-Jing,Zhang, De-Long
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p. 8346 - 8355
(2020/10/06)
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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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- Recognition of Al3+ through the off-on mechanism as a proficient driving force for the hydrolysis of BODIPY conjugated Schiff base and its application in bio-imaging
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Two new BODIPY azine bearing quinoline and pyrazine attached Schiff base chemosensors (R1 and R2) have been synthesized and applied for the detection of Al3+ in CH3CN/H2O medium. Intramolecular hydrogen bonding makes both the sensors rigid and helps to encapsulate Al3+ in the cavity. The pink colour of R1 and R2 has been changed to green fluorescent upon excess addition of Al3+ which is only because of the hydrolysis of imine bond to regenerate compound 8. Another nitrogen atom present in quinoline and in pyrazine moiety made R1 and R2 more efficient in sensing of Al3+ ion compare to R1D, R2B and R2D. Cell viability and fluorescence microscopic experiments showed that the chemosensors are cytocompatible and can be used as an effective fluorescent probe for detecting Al3+ ion in the living cell.
- Kashyap, Kumari Somlata,Kumar, Ashish,Hira, Sumit Kumar,Dey, Swapan
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- A Facile Synthesis of Substituted 2-(5-(Benzylthio)-1,3,4-oxadiazol-2-yl)pyrazine Using Microwave Irradiation and Conventional Method with Antioxidant and Anticancer Activities
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A series of novel substituted 2-(5-(benzylthio)-1,3,4-oxadiazol-2-yl)pyrazine derivatives (6a–n) were synthesized under microwave irradiation and conventional conditions with less reaction time with good to excellent yields. All the synthesized compounds were screened for antioxidant and anticancer activities. Out of the 14 prepared derivatives, compounds 6f and 6m were most potent and active with antioxidant and anticancer activities, respectively. Also, the developed technique was simple, easy, and less time consuming.
- Patil, Sanjeev R.,Sarkate, Aniket P.,Karnik, Kshipra S.,Arsondkar, Ashish,Patil, Vrushali,Sangshetti, Jaiprakash N.,Bobade, Anil S.,Shinde, Devanand B.
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p. 859 - 866
(2019/02/01)
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- Design, synthesis, anti-mycobacterial and cytotoxic evaluation of C-4 functionalized 1,8-naphthalimide-heterocyclic hydrazide conjugates
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This manuscript discloses the design and synthesis of a series of C-4 functionalized 1,8-naphthalimide-heterocyclic hydrazide conjugates along with their anti-mycobacterial and cytotoxic evaluation. The present work assumes significance as it describes the first report on the amalgamation of C-4 substituted naphthalimides with various heterocyclic hydrazides. However, contrary to the rationale behind the synthesis of the conjugates, none of them inhibited the growth of Mycobacterium tuberculosis at the tested concentrations though these were non-cytotoxic towards the Vero kidney epithelial cell line.
- Shalini,Johansen, Matt D.,Kremer, Laurent,Kumar, Vipan
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p. 1300 - 1305
(2019/03/14)
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- ATF6 INHIBITORS AND USES THEREOF
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Compounds as inhibitors of Activating Transcription Factor 6 (ATF6) are provided. The compounds may find use as therapeutic agents for the treatment of diseases or disorders mediated by ATF6 and may find particular use in the treatment of viral infections, neurodegenerative diseases, vascular diseases, or cancer.
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- Application of self-assembled nano fluorescent probe for selective detection of human serum albumin
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The invention discloses a novel self-assembled nanoparticle formed by a hydrazide Schiff base and used as a fluorescent probe. The hydrazide Schiff base is self-assembled into a nano system in a PBS buffer, and the nano system can be used for qualitative and quantitative detection of human serum albumin (HSA). The advantage of the probe is that: based on a mechanism of self-assembly and twisted intramolecular charge transfer, the probe itself has almost no fluorescence signal, and has obvious fluorescence enhancement after interaction with a substance to be detected. A synthesis route of the probe is simple and convenient, yield is high, the nano system is formed uniformly and fast by self-assembly, selectivity of a substance to be detected is good, and sensitivity is high. The self-assembled nano fluorescent probe can be used for detecting HSA in biological and clinical test samples, and has good application prospects.
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- HETEROARYL-SUBSTITUTED TRIAZOLES AS APJ RECEPTOR AGONISTS
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Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.
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Paragraph 0668; 0674
(2018/06/12)
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- Design, Synthesis and Evaluation of Antitubercular Activity of Novel 1,2,4-Triazoles Against MDR Strain of Mycobacterium tuberculosis
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Emergence of various forms of resistant strains of Mycobacterium tuberculosis led to the exploration of drugs with novel mechanism of action. Recently econazole, an azole based antitubercular agent, attracted major attention for targeting mycobacterial cytochrome P450. In the present study, we designed novel 1,2,4-triazole derivatives based on econazole moiety and evaluated them for in vitro antitubercular activity against M. tuberculosis H37Rv and multi-drug resistant (MDR) strains of Mycobacterium.
- Ganesh Kumar,Gautham Shenoy,Kar, Sidhartha Sankar,Shenoy, Vishnu,Bairy, Indira
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p. 907 - 917
(2018/02/07)
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- Synthesis, spectroscopic analyses, chemical reactivity and molecular docking study and anti-tubercular activity of pyrazine and condensed oxadiazole derivatives
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The FT-IR spectral analysis and theoretical calculations of the wavenumbers of three oxadiazole derivatives, 2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (ORTHOPHPZ), 2-(5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (METAPHPZ) and 2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (PARAPHPZ) were reported in the present work. The theoretically predicted values of polarizability give the nonlinear behaviour of the compounds. The frontier molecular orbital analysis show the chemical stability of the title compounds and the NBO analysis gives the interactions in the molecular systems. Understanding of reactivity of newly synthetiszed oxadiazole derivatives in this study has been achieved thanks to combination of density functional theory (DFT) calculations, molecular dynamics (MD) simulations and molecular docking procedures. New oxadiazole derivatives have also been characterized experimentally through FT-IR and NMR approaches, thanks to which detailed structural properties have been understood. Both global and local reactivity properties have been investigated by calculations of quantum molecular descriptors such as molecular electrostatic potential (MEP), local average ionization energy (ALIE), Fukui functions, bond dissociation energies for hydrogen abstraction (H-BDE), radial distribution functions and binding energies of ligand against selected protein. The first hyperpolarizabilities of ORTHOPHPZ, METAPHPZ and PARAPHPZ are respectively, 84.62, 94.71 and 184.10 times that of urea. The docked ligands form stable complexes with the receptor 1-phosphatidylinositol phosphodiesterase and the results suggest that these compounds can be developed as new anti-cancer drugs. The anti-TB activity of PM series against M. tuberculosis H37RV strain was performed by Middlebrooke 7H-9 method. The compounds, ORTHOPHPZ, METAPHPZ and PARAPHPZ were moderately active between 25 and 50 μg/ml concentration as compared with the standard anti-TB agents and the –log MIC activity was found in the range of 1.011–1.274 as compared with isoniazid (INH) (1.137) and pyrazinamide (PZA) (1.115) standard anti-TB agents.
- Al-Tamimi, Abdul-Malek S.,Mary, Y. Sheena,Miniyar, Pankaj B.,Al-Wahaibi, Lamya H.,El-Emam, Ali A.,Armakovi?, Stevan,Armakovi?, Sanja J.
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p. 459 - 469
(2018/05/29)
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- Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities
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Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Nitro substitution had both negative and positive effects on the examined properties, and we identified new structure-activity relationships. Naphthyl and biphenyl derivatives showed selective antiproliferative action, particularly in the breast adenocarcinoma MCF-7 cell line, where they exceeded the selectivity of the parent compound NHAPI. Of particular interest is a compound prepared from 2-hydroxy-5-methyl-3-nitroacetophenone and biphenyl-4-carbohydrazide, which protected cardiomyoblasts against oxidative injury at 1.8 ± 1.2 μM with 24-fold higher selectivity than SIH. These compounds will serve as leads for further structural optimization and mechanistic studies.
- Hru?ková, Kate?ina,Pot??ková, Eli?ka,Opálka, Luká?,Hergeselová, Tereza,Ha?ková, Pavlína,Kova?íková, Petra,?im?nek, Tomá?,Vávrová, Kate?ina
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p. 435 - 446
(2018/05/29)
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- Antileishmanial potential of fused 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiols: Synthesis, biological evaluations and computational studies
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A series of newer 1,2,4-triazole-3-thiol derivatives 5(a–m) and 6(a–i) containing a triazole fused with pyrazine moiety of pharmacological significance have been synthesized. All the synthesized compounds were screened for their in vitro antileishmanial and antioxidant activities. Compounds 5f (IC50?=?79.0?μM) and 6f (IC50?=?79.0?μM) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50?=?490.0?μM). Compounds 5b (IC50?=?13.96?μM) and 6b (IC50?=?13.96?μM) showed significant antioxidant activity. After performing molecular docking study and analyzing overall binding modes it was found that the synthesized compounds had potential to inhibit L. donovani pteridine reductase 1 enzyme. In silico ADME and metabolic site prediction studies were also held out to set an effective lead candidate for the future antileishmanial and antibacterial drug discovery initiatives.
- Patil, Sanjeev R.,Asrondkar, Ashish,Patil, Vrushali,Sangshetti, Jaiprakash N.,Kalam Khan, Firoz A.,Damale, Manoj G.,Patil, Rajendra H.,Bobade, Anil S.,Shinde, Devanand B.
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supporting information
p. 3845 - 3850
(2017/07/27)
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- 1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-β-lactamases
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Metallo-β-lactamases (MBLs) cause resistance of Gram-negative bacteria to β-lactam antibiotics and are of serious concern, because they can inactivate the last-resort carbapenems and because MBL inhibitors of clinical value are still lacking. We previously identified the original binding mode of 4-amino-2,4-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione (compound IIIA) within the dizinc active site of the L1 MBL. Herein we present the crystallographic structure of a complex of L1 with the corresponding non-amino compound IIIB (1,2-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione). Unexpectedly, the binding mode of IIIB was similar but reverse to that of IIIA. The 3 D structures suggested that the triazole–thione scaffold was suitable to bind to the catalytic site of dizinc metalloenzymes. On the basis of these results, we synthesized 54 analogues of IIIA or IIIB. Nineteen showed IC50 values in the micromolar range toward at least one of five representative MBLs (i.e., L1, VIM-4, VIM-2, NDM-1, and IMP-1). Five of these exhibited a significant inhibition of at least four enzymes, including NDM-1, VIM-2, and IMP-1. Active compounds mainly featured either halogen or bulky bicyclic aryl substituents. Finally, some compounds were also tested on several microbial dinuclear zinc-dependent hydrolases belonging to the MBL-fold superfamily (i.e., endonucleases and glyoxalase II) to explore their activity toward structurally similar but functionally distinct enzymes. Whereas the bacterial tRNases were not inhibited, the best IC50 values toward plasmodial glyoxalase II were in the 10 μm range.
- Sevaille, Laurent,Gavara, Laurent,Bebrone, Carine,De Luca, Filomena,Nauton, Lionel,Achard, Maud,Mercuri, Paola,Tanfoni, Silvia,Borgianni, Luisa,Guyon, Carole,Lonjon, Pauline,Turan-Zitouni, Gülhan,Dzieciolowski, Julia,Becker, Katja,Bénard, Lionel,Condon, Ciaran,Maillard, Ludovic,Martinez, Jean,Frère, Jean-Marie,Dideberg, Otto,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
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p. 972 - 985
(2017/06/27)
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- Antimicrobial activity of organometallic isonicotinyl and pyrazinyl ferrocenyl-derived complexes
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Isonicotinyl and pyrazinyl ferrocenyl-derived complexes were prepared using various hydrazides and ferrocenyl aldehydes. Three heterobimetallic complexes were also synthesized from the Schiff base-derived isonicotinyl ferrocene complex using various platinum group metal dimers based on ruthenium, rhodium and iridium. All complexes were evaluated in vitro for antimycobacterial and antiparasitic activity. Against Mycobacterium tuberculosis H37Rv, the platinum group metal complexes showed glycerol-dependent antimycobacterial activity. The antiplasmodial activities against the NF54 chloroquine-sensitive strain of Plasmodium falciparum of some compounds were moderate, while some complexes also showed promising activity against Trichomonas vaginalis. Incorporation of the ferrocenyl-salicylaldimine moiety resulted in enhanced antimicrobial activity compared to the non-ferrocenyl compound in some cases. The bimetallic iridium-ferrocene isonicotinyl complex exhibited superior antitrichomonal activity relative to its organic counterpart, isoniazid. Furthermore, all these compounds, when screened on several normal flora bacteria of humans, showed no effect on the microbiome, emphasizing the selection of these compounds for these pathogens. The promising antimicrobial activities of the complexes thus supports incorporation of ferrocene as part of existing antimicrobial therapies in order to alter their biological activities favorably.
- Stringer, Tameryn,Seldon, Ronnett,Liu, Nicole,Warner, Digby F.,Tam, Christina,Cheng, Luisa W.,Land, Kirkwood M.,Smith, Peter J.,Chibale, Kelly,Smith, Gregory S.
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p. 9875 - 9885
(2017/08/09)
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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; 0237; 0238; 0239
(2017/01/02)
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- Synthesis and biological evaluation of novel resveratrol-oxadiazole hybrid heterocycles as potential antiproliferative agents
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A novel class of resveratrol-oxadiazole hybrid compounds was synthesized to screen for their in vitro antiproliferative activity against three human cancer cell lines. All the compounds showed superior antiproliferative activity than the reference compound resveratrol. The most promising active compounds in this series were 1g, 2g, 1c, 2c, 2i and 1a (GI50 0.1 μM), endowed with excellent antiproliferative activity. Thus, we believe that resveratrol-oxadiazole hybrid compounds may possibly be used as a good leads for the development of new antiproliferative agents. Structures of newly synthesized compounds were confirmed by NMR and IR spectral data.
- Murty,Penthala, Raju,Polepalli, Sowjanya,Jain
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p. 627 - 643
(2016/03/08)
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- Synthesis and docking studies of pyrazine-thiazolidinone hybrid scaffold targeting dormant tuberculosis
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The persistence of Mycobacterium tuberculosis (MTB) in dormant stage assists the pathogen to develop resistance against current antimycobactrial drugs. To address this issue, we report herein the synthesis of N-(4-oxo-2 substituted thiazolidin-3yl) pyrazi
- Chitre,Asgaonkar,Miniyar,Dharme,Arkile,Yeware,Sarkar,Khedkar,Jha
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supporting information
p. 2224 - 2228
(2016/04/20)
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- Aroylhydrazone iron chelators: Tuning antioxidant and antiproliferative properties by hydrazide modifications
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Aroylhydrazones such as salicylaldehyde isonicotinoyl hydrazone (SIH) are tridentate iron chelators that may possess antioxidant and/or antineoplastic activities. Their main drawback, their low stability in plasma, has recently been partially overcome by exchanging the aldimine hydrogen for an unbranched alkyl group. In this study, ten analogs of methyl- and ethyl-substituted SIH derivatives with modified hydrazide scaffolds were synthesized to further explore their structure-activity relationships. Their iron-chelation efficiencies, anti- or pro-oxidant potentials, abilities to induce protection against model oxidative injury on the H9c2 cell line derived from rat embryonic cardiac tissue, cytotoxicities on the same H9c2 cells and antiproliferative activities on MCF-7 human breast adenocarcinoma and HL-60 human promyelotic leukemia cell lines were evaluated. Compounds derived from lipophilic naphthyl and biphenyl hydrazides displayed highly selective antiproliferative activities against both MCF-7 and HL-60 cell lines, and they showed markedly improved stabilities in plasma compared to SIH. Of particular interest is a hydrazone prepared from 2-hydroxypropiophenone and pyridazin-4-carbohydrazide that showed a considerable antiproliferative effect and protected cardiomyoblasts against oxidative stress with a five-fold higher selectivity compared to the parent compound SIH. Thus, this work highlighted new structure-activity relationships among antiproliferative and antioxidant aroylhydrazones and identified new lead compounds for further development.
- Hru?ková, Kate?ina,Pot??ková, Eli?ka,Hergeselová, Tereza,Liptáková, Lucie,Ha?ková, Pavlína,Mingas, Panagiotis,Kova?íková, Petra,?im?nek, Tomá?,Vávrová, Kate?ina
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- Tryptophan and thiosemicarbazide derivatives: Design, synthesis, and biological evaluation as potential β-D-galactosidase and β-D-glucosidase inhibitors
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Glycosidases, including β-D-galactosidase and β-D-glucosidase, are involved in a range of metabolic disorders, such as cancer, viral or bacterial infections, and diabetes. Previously, we scanned the pharmacophoric space of these enzymes and had a self-consistent and predictive quantitative structure-activity relationship that was used to identify several β-D-galactosidase and β-D-glucosidase inhibitors via in silico search of structural databases. Guided by the preceding modeling efforts, synthesis of a series of tryptophan and thiosemicarbazide derivatives as β-D-galactosidase and β-D-glucosidase inhibitors that match the generated pharmacophores followed by in vitro bioassay was carried out. Synthesized compounds 3c (37 % inhibition at 100 μM) and 4d (49 % inhibition at 100 μM) exhibited the best inhibitory bioactivities against β-D-galactosidase and β-D-glucosidase, respectively. They can serve as a promising lead compounds for the development of potential glycosidase inhibitors.
- Abu Khalaf, Reema,Abdula, Ahmed Mutanabbi,Mubarak, Mohammad S.,Taha, Mutasem O.
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p. 2529 - 2550
(2015/06/22)
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- Design, synthesis and antibacterial activities of 5-(pyrazin-2-yl)-4H-1,2, 4-triazole-3-thiol derivatives containing Schiff base formation as FabH inhibitory
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A series of novel schiff base derivatives (H1-H20) containing pyrazine and triazole moiety have been designed and synthesized, and their biological activities were also evaluated as potential inhibitors of β-ketoacyl-acyl carrier protein synthase III (FabH). These compounds were assayed for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis and Bacillus amyloliquefaciens and selected compounds among them were tested for their Escherichia coli FabH inhibitory activity. Based on the biological data, compound H17 showed the most potent antibacterial activity with MIC values of 0.39-1.56 μg/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC50 of 5.2 μM, being better than the positive control Kanamycin B with IC50 of 6.3 μM. Furthermore, docking simulation was performed to position compound H17 into the E. coli FabH active site to determine the probable binding conformation. This study indicated that compound H17 has demonstrated significant E. coli FabH inhibitory activity as a potential antibacterial agent and provides valuable information for the design of E. coli FabH inhibitors.
- Zhang, Fei,Wen, Qing,Wang, She-Feng,Shahla Karim, Baloch,Yang, Yu-Shun,Liu, Jia-Jia,Zhang, Wei-Ming,Zhu, Hai-Liang
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- Design, synthesis and biological evaluation of heterocyclic azoles derivatives containing pyrazine moiety as potential telomerase inhibitors
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Three series of novel heterocyclic azoles derivatives containing pyrazine (5a-5k, 8a-8k and 11a-11k) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential telomerase inhibitors. Among the oxadiazole derivatives, compound 5c showed the most potent biological activity against SW1116 cancer cell line (IC50 = 2.46 μM against SW1116 and IC50 = 3.55 μM for telomerase). Compound 8h performed the best in the thiadiazole derivatives (IC50 = 0.78 μM against HEPG2 and IC50 = 1.24 μM for telomerase), which was comparable to the positive control. While compound 11f showed the most potent biological activity (IC50 = 4.12 μM against SW1116 and IC50 = 15.03 μM for telomerase) among the triazole derivatives. Docking simulation by positioning compounds 5c, 8h and 11f into the telomerase structure active site was performed to explore the possible binding model. The results of apoptosis demonstrated that compound 8h possessed good antitumor activity against HEPG2 cancer cell line. Therefore, compound 8h with potent inhibitory activity in tumor growth inhibition may be a potential antitumor agent against HEPG2 cancer cell. Therefore, the introduction of oxadiazole, thiadiazole and triazole structures reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.
- Zhang, Yan-Bin,Wang, Xiao-Liang,Liu, Wen,Yang, Yu-Shun,Tang, Jian-Feng,Zhu, Hai-Liang
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p. 6356 - 6365
(2012/11/07)
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- Electrochemical and spectroscopic investigations of isoniazide and its analogs with ds.DNA at physiological pH: Evaluation of biological activities
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Interaction and binding of isonicotinic acid hydrazide (INH) and its two analogs; pyrazine carboxylic acid hydrazide (PCH) and 2,4-dihydroxy benzoic acid hydrazide (2,4-DHBAH) with DNA has been investigated by UV-spectroscopy and cyclic voltammetry (CV) a
- Arshad, Nasima,Yunus, Uzma,Razzque, Shumaila,Khan, Maliha,Saleem, Samreen,Mirza, Bushra,Rashid, Naghmana
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experimental part
p. 452 - 461
(2012/03/26)
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- Quadruple-CO32- bridged octanuclear dysprosium(iii) compound showing single-molecule magnet behaviour
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A novel octanuclear dysprosium(iii) compound, templated by quadruple μ4-CO32- introduced via spontaneous fixation of atmospheric carbon dioxide, shows single-molecule-magnet behaviour with an obvious hysteresis loop detect
- Tian, Haiquan,Zhao, Lang,Guo, Yun-Nan,Guo, Yang,Tang, Jinkui,Liu, Zhiliang
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supporting information; experimental part
p. 708 - 710
(2012/02/01)
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- Dinuclear, tetranuclear and chain (MnII, CoII) complexes of multifunctional hydrazone ligands- Structural and magnetic studies
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The coordination chemistry of a group of hydrazone-based ligands, modified with carboxylate and heterocyclic terminal donor groups, with MnII and CoII has been investigated. The multifunctional nature of the ligands allows coordinative flexibility based on the hydrazone core, which is well established to lead to spin-coupled polymetallic assemblies through μ-Ohydrazone bridging. Examples of dinuclear, tetranuclear and chain complexes are reported with hydrazone, carboxylate and triazole bridging. Spin exchange through the μ-O and μ-N,N bridging connections leads to antiferromagnetic exchange in most cases, except for the central subunit in the MnII4 chain complex, where small ( 90°) bridge angles result in contributing ferromagnetic interactions. Multifunctional polytopic hydrazone ligands form polymetallic complexes with μ-O (hydrazone, carboxylate) and μ-N,N (triazole) bridging, leading to spin-spin interactions between the metal centres with examples of antiferromagnetic and ferromagnetic exchange.
- Bettle, Peter J.,Dawe, Louise N.,Anwar, Muhammad U.,Thompson, Laurence K.
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p. 5036 - 5042
(2012/01/14)
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- Synthesis and antimycobacterial evaluation of N'-(E)- heteroaromaticpyrazine-2-carbohydrazide derivatives
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A series of nine N'-(E)-heteroaromatic-pyrazine-2-carbohydrazide derivatives (5a-f and 6a-c) have been synthesized and evaluated against M. tuberculosis ATCC 27294 using the micro plate Alamar Blue assay (MABA), being the activities expressed as the minim
- Lima,Henriques,Candea,Lourenco,Bezerra,Ferreira,Kaiser,De Souza
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experimental part
p. 245 - 249
(2012/05/05)
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- Synthesis and cytotoxic evaluation of disubstituted N-acylhydrazones pyrazinecarbohydrazide derivatives
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A series of seventeen disubstituted N-acylhydrazone pyrazinecarbohydrazide (4-20) have been synthesized and evaluated for their cell viabilities, were compared to another monosubstituted derivatives previously synthesized by us. This study indicated that the position and nature of the substituents in the aromatic ring influence the cytotoxicity of this series.
- De Ferreira, Marcelle L.,Candea, Andre L. P.,Henriques, Maria Das Gracas M. De O.,Kaiser, Carlos R.,Lima, Camilo H. Da S.,De Souza, Marcus V. N.
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p. 275 - 280
(2011/03/18)
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- Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates
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In this paper, we report the synthesis and pharmacological evaluation of pyrazine N-acylhydrazone (NAH) derivatives (2a-s) designed as novel analgesic and anti-inflammatory drug candidates. This series was planned by molecular simplification of prototype
- Silva, Yolanda Karla Cupertino Da,Augusto, Cristina Villarinho,Barbosa, Maria Leticia De Castro,Melo, Gabriela Muniz De Albuquerque,Queiroz, Aline Cavalcanti De,Dias, Thays De Lima Matos Freire,Junior, Walfrido Bispo,Barreiro, Eliezer J.,Lima, Lidia Moreira,Alexandre-Moreira, Magna Suzana
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experimental part
p. 5007 - 5015
(2010/09/05)
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- Synthesis andanti-mycobacterial evaluation of some pyrazine-2-carboxylic acid hydrazide derivatives
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A series of pyrazine-2-carboxylic acid hydrazide derivatives were synthesized and screened for their activity against Mycobacterium tuberculosis. The results show that pyrazine-2-carboxylic acid hydrazi-deehydrazone derivatives 3ael were less active than pyrazinamide. In contrast,the N 4-ethyl-N1-pyr-azinoyl-thiosemicarbazide 4 showed the highest activity against M. tuberculosis H37Rv (IC90 16.87 mg/mL). Details of the structureeactivity and structureecytotoxicity relationships are discussed.
- Abdel-Aziz, Mohamed,Bdel-Rahman, Hamdy M.A.
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experimental part
p. 3384 - 3388
(2010/08/13)
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- 5,6,7,8-TETRAHYDRO[1,2,4]TRIAZOLO[4,3-a]PYRAZINE DERIVATIVES AS P2X7 MODULATORS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6 R7, optionally substituted heteroaryl (Het), or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.
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Page/Page column 125-126
(2010/11/17)
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- Synthesis and antimycobacterial activity of N′-[(E)-(monosubstituted-benzylidene)]-2-pyrazinecarbohydrazide derivatives
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The present article describes a series of twenty-six N′-[(E)-(monosubstituted-benzylidene)]-2-pyrazinecarbohydrazide (4-29), which were synthesized and evaluated for their cell viabilities in non infected and infected macrophages with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). Afterwards, the non-cytotoxic compounds (4, 6, 8, 15, 21, 23, 24, 27 and 28) were assessed against Mycobacterium tuberculosis ATCC 27294 using the micro plate Alamar Blue assay (MABA) and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. The compounds 6, 23, 27 and 28 exhibited a significant activity (50-100 μg/mL) when compared with first line drugs such as pyrazinamide and were not cytotoxic in their respective MIC values.
- Vergara, Fatima M.F.,Lima, Camilo H. da S.,Henriques, Maria das Gracas M. de O.,Candea, Andre L.P.,Lourenco, Maria C.S.,Ferreira, Marcelle de L.,Kaiser, Carlos R.,de Souza, Marcus V.N.
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experimental part
p. 4954 - 4959
(2010/02/27)
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- MGluR5 modulators I
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The present invention is directed to novel compounds, to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds.
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Page/Page column 26
(2008/06/13)
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- SUBSTITUTED HETEROCYCLES AND THE USES THEREOF
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This invention relates to novel compounds having the structural formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment or prophylaxis of cancer.
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Page/Page column 128
(2010/02/12)
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- Synthesis and SAR evaluation of 1,2,4-triazoles as A2A receptor antagonists
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The synthesis and in vitro structure-activity relationships (SAR) of a series of triazoles as A2A receptor antagonists is reported. This resulted in the identification of potent, selective and permeable 1,2,4-triazoles such as 42 for further op
- Alanine, Alexander,Anselm, Lilli,Steward, Lucinda,Thomi, Stefan,Vifian, Walter,Groaning, Michael D.
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p. 817 - 821
(2007/10/03)
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- Ruthenium(II) and osmium(II) polypyridyl complexes of an asymmetric pyrazinyl- and pyridinyl-containing 1,2,4-triazole based ligand. Connectivity and physical properties of mononuclear complexes
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The synthesis, purification and characterisation of two coordination isomers of ruthenium(II) and osmium (II) complexes containing the ligand 3-(pyrazin-2′-yl)-5-(pyridin-2′-yl)-1,2,4-triazole (Hppt) are described. The X-ray and molecular structure of the complex [Ru(bipy)2(ppt)]PF6·CH3OH (1a) is reported, where the Ru(bipy)2-centre is bound to the ppt- ligand via the pyridine nitrogen and the N1 atom of the triazole ring. 1H NMR spectroscopic measurements confirm that in the second isomer (1b) the Ru(bipy)2-moiety is bound via the N2 atom of the triazole ring and the pyrazine ring. Partially deuteriated metal complexes are utilised to facilitate interpretation of 1H NMR spectra. The redox and electronic properties indicate that there are significant differences in the electronic properties of the two coordination isomers obtained. The acid-base properties of the compounds are also reported and show that the pKa of the 1,2,4-triazole ring varies systematically depending on the nature of the non-coordinating substituent. Analysis of these data indicates a significant electronic interaction between the pyridyl/pyrazyl rings and the 1,2,4-triazole ring in the coordinated ppt- ligand.
- Browne, Wesley R.,O'Connor, Christine M.,Hughes, Helen P.,Hage, Ronald,Walter, Olaf,Doering, Manfred,Gallagher, John F.,Vos, Johannes G.
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p. 4048 - 4054
(2007/10/03)
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