TY - JOUR
T1 - One-pot synthesis of dihydropyridine carboxylic acids via functionalization of 3-((trimethylsilyl)ethynyl)pyridines and an unusual hydration of alkynes
T2 - Molecular docking and antifungal activity
AU - Ballinas-Indilí, Ricardo
AU - Gómez-García, Omar
AU - Treviño-Crespo, Eric
AU - Andrade-Pavón, Dulce
AU - Villa-Tanaca, Lourdes
AU - Toscano, Ruben A.
AU - Álvarez-Toledano, Cecilio
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/4/23
Y1 - 2021/4/23
N2 - 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.
AB - 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.
KW - Antifungal activity
KW - Candida spp
KW - Dihydropyridines
KW - Hydration of alkynes
KW - Molecular docking
UR - http://www.scopus.com/inward/record.url?scp=85103261902&partnerID=8YFLogxK
U2 - 10.1016/j.tet.2021.132086
DO - 10.1016/j.tet.2021.132086
M3 - Artículo
AN - SCOPUS:85103261902
SN - 0040-4020
VL - 86
JO - Tetrahedron
JF - Tetrahedron
M1 - 132086
ER -