One-pot synthesis of dihydropyridine carboxylic acids via functionalization of 3-((trimethylsilyl)ethynyl)pyridines and an unusual hydration of alkynes: Molecular docking and antifungal activity

Abstract

Activation of 3-((trimethylsilyl)ethynyl)pyridine with triflic anhydride followed by nucleophilic addition of bis(trimethylsili) ketene acetals and a unusual alkyne hydration allowed to obtain new series of 3-acetylated dihydropyridine acids 3a-h in a single step. Secondly, docking studies were conducted on four of the test compounds ( 3b , 3e , 17a and 17b ) and a reference drug (fluconazole) at the active site of lanosterol 14α-demethylase enzymes (CYP51) from Candida spp., in vitro inhibition assays were performed with the same compounds and yeast species. Compounds 3b , 3e , 17a and 17b interacted with key amino acids of the active site of CYP51 enzymes in a similar manner as fluconazole. Compared to fluconazole, the test compounds showed better binding energy values (−4.84 to −9.1 vs. −1.51 to 5.68 kcal/mol) and in vitro antifungal activity (lower MIC values) on different Candida species. Hence, the dihydropyridine derivatives can be considered candidates for the development of new antifungal drugs. • Dihydropyridines. • Hydration of alkynes. • Molecular docking. • antifungal activity. • Candida spp.