917078-24-1Relevant articles and documents
Design and synthesis of new fluconazole analogues
Pore, Vandana S.,Agalave, Sandip G.,Singh, Pratiksha,Shukla, Praveen K.,Kumar, Vikash,Siddiqi, Mohammad I.
, p. 6551 - 6561 (2015)
We have synthesized new fluconazole analogues containing two different 1,2,3-triazole units in the side chain. The synthesis of new amide analogues using a variety of acids is also described. All the compounds showed very good antifungal activity. A hemol
Synthesis and biological evaluation of new fluconazole β-lactam conjugates linked via 1,2,3-triazole
Divse, Jaisingh M.,Mhaske, Santosh B.,Charolkar, Chaitanya R.,Sant, Duhita G.,Tupe, Santosh G.,Deshpande, Mukund V.,Khedkar, Vijay M.,Nawale, Laxman U.,Sarkar, Dhiman,Pore, Vandana S.
, p. 470 - 479 (2017/02/05)
Novel 1,2,3-triazole-linked β-lactam-fluconazole conjugates 12(a-l) were designed and synthesized. The compounds showed potent antifungal activity against two pathogenic Candida strains; Candida albicans ATCC 24433 and Candida albicans ATCC 10231 with MIC values in the range of 0.0625-2 μg mL-1. Compounds 12h, 12j and 12k showed promising antifungal activity against all the tested fungal pathogens except C. neoformans ATCC 34554 compared to fluconazole. Compound 12j in which the β-lactam ring was formed using para-anisidine and benzaldehyde was found to be more potent than fluconazole against all the fungal strains with an IC50 value of -1 for Candida albicans (ATCC 24433). Mechanistic studies for active compounds revealed that the antifungal action was due to ergosterol inhibition. Compounds 12h and 12j at a concentration of 0.125 μg mL-1 caused 91.5 and 96.8% ergosterol depletion, respectively, compared to fluconazole which at the same concentration caused 49% ergosterol depletion. The molecular docking study revealed that all the fluconazole β-lactam conjugates 12(a-l) could snugly fit into the active site of lanosterol 14α-demethylase (CYP51) with varying degrees of affinities. As anticipated, the binding energy for compound 12j (-58.961 kcal mol-1) was much smaller than that for fluconazole (-52.92 kcal mol-1). The synthesized compounds have therapeutic potential for the control of candidemia.
Synthesis, in Vitro Biological Evaluation, and Molecular Docking of New Triazoles as Potent Antifungal Agents
Li, Xiang,Liu, Chao,Tang, Sheng,Wu, Qiuye,Hu, Honggang,Zhao, Qingjie,Zou, Yan
, p. 42 - 49 (2016/01/29)
Based on the structure of the active site of CYP51 and the structure-activity relationships of azole antifungal compounds that we designed in a previous study, a series of 1-{1-[2-(substitutedbenzyloxy)ethyl]-1H-1,2,3-triazol-4-yl}-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols (6a-n) were designed and synthesized utilizing copper-catalyzed azide-alkyne cycloaddition. Preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent antifungal activities with a broad spectrum in vitro. Molecular docking results indicated that the interaction between the title compounds and CYP51 comprised π-π interactions, hydrophobic interactions, and the narrow hydrophobic cleft.
