02332nas a2200241   4500008004100000245010600041210007000147260000800217300001200225490000700237520147700244100002401721700002401745700002901769700002101798700002201819700002601841700002301867700002301890700001901913700002201932856013601954       2017                        eng d00aSynthesis and biological evaluation of new fluconazole β-lactam conjugates linked via 1,2,3-triazole0 aSynthesis and biological evaluation of new fluconazole βlactam c  cFEB  a470-4790 v413 a<p>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 &lt;0.015 μg mL−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.</p>1 aDivse, Jaisingh, M.1 aMhaske, Santosh, B.1 aCharolkar, Chaitanya, R.1 aSant, Duhita, G.1 aTupe, Santosh, G.1 aDeshpande, Mukund, V.1 aKhedkar, Vijay, M.1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aPore, Vandana, S.  uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-new-fluconazole-%CE%B2-lactam-conjugates-linked-123-triazole