6164-79-0Relevant articles and documents
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
Zhang, Fei,Wen, Qing,Wang, She-Feng,Shahla Karim, Baloch,Yang, Yu-Shun,Liu, Jia-Jia,Zhang, Wei-Ming,Zhu, Hai-Liang
, p. 90 - 95 (2014)
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.
Cobalt and silver complexes of terdentate pyrazine-based amide ligands and assembly of monocobalt building blocks through a silver connector
Hellyer, Ryan M.,Larsen, David S.,Brooker, Sally
, p. 1162 - 1171 (2009)
Two terdentate pyrazine-based amide ligands have been prepared from methyl pyrazine-2-carboxylate and 2-(amino-methyl)pyridine (HL1M) or 2- 2-aminoethyl)pyridine (HL1E) in order to probe the potential of the "spare" nitrogen atom "out: the back" of the pyrazine ring to coordinate to a different metal ion and thereby act as a linker between complexes. Two inert cobalt(III) complexes, [CoIII(L 1M)2](BF4) 1/4H2O and Co III(L1E)2](BF4)-1/2H20, have been prepared as building blocks and the silver(I) coordination of the ligands also probed, forming {[AgI(HL1M)]BF 4}∞, and [AgI2(HL1LE) 2]- (BF4)2. The [CoIII(L 1E)2](BF4) building block has been successfully connected to a second such complex by coordination of silver(I) to a "spare" pyrazine nitrogen atom on each complex, resulting in [{Co III(L1E)2}2AgI](BF 4)(N03)2, All five complexes have been structurally characterised. Mass spectra and cyclic voltammetry studies on "aged" (kept in solution in air for 2 d) samples clearly showed that the cobalt complex of the methylene-linked ligand was prone to slow ligand oxidation, forming [CoIII(L1Mox)(L1M)](BF 4) and [CoIII(L1Mox)2](BF 4). Fresh samples of [CoIII(L1M) 2](BF4)-1/4H20 and oIII(L 1M)2](BF4)-1/2H20 undergo a chemically reversible one- electron reduction in dry acetonitrile, at -0.71 and -0.48 V vs. 0.01 M AgN03/Ag, respectively, consistent with the methylene-linked ligand being better able to stabilise the higher oxidation state of cobalt than the ethylene-linked ligand.
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Marx,Spoerri
, p. 111 (1972)
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New silver(I) phosphino complexes: Evaluation of their potential as prospective agents against Mycobacterium tuberculosis
Gambino, Dinorah,Maldonado, Yndira Dolores,Manieri, Karyn Fernanda,Pavan, Fernando R.,Scalese, Gonzalo,Aguirre Méndez, Larry D.
, (2021/12/14)
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.
1H-1,2,3-triazole embedded Isatin-Benzaldehyde-bis(heteronuclearhydrazones): design, synthesis, antimycobacterial, and cytotoxic evaluation
Johansen, Matt D.,Kremer, Laurent,Kumar, Sumit,Kumar, Vipan,Preeti,Sharma, Bharvi
, (2021/12/09)
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.
