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

• Published in: Tetrahedron Vol. 86; pp. 132086 - 132101
• Main Authors: Ballinas-Indilí, Ricardo, Gómez-García, Omar, Treviño-Crespo, Eric, Andrade-Pavón, Dulce, Villa-Tanaca, Lourdes, Toscano, Ruben A., Álvarez-Toledano, Cecilio
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 23.04.2021; Elsevier
• Subjects: Antifungal activity; Candida spp; Chemistry; Chemistry, Organic; Dihydropyridines; Hydration of alkynes; Molecular docking; Physical Sciences; Science & Technology; Candida spp; Antifungal activity; Dihydropyridines; Hydration of alkynes; Molecular docking
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2021.132086

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. [Display omitted] •Dihydropyridines.•Hydration of alkynes.•Molecular docking.•antifungal activity.•Candida spp.