Synthesis, antifungal activity, and molecular docking study of some novel highly substituted 3-indolylthiophene derivatives

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Abstract

Background and objectives
The currently available antifungal drugs have the limitations of toxicity, potential drug interaction with other drugs, insufficient pharmacokinetics properties, and development of resistance. Thus, development of new antifungal agents with less toxicity is urgently required. The present work aimed to synthesize new 3-indolylthiophene derivatives and evaluate their antifungal activity by studying their molecular docking.
Materials and methods
New series of thiadiazoles , morpholinyl-acetamides , 4-methylpiperazinylacetamides , thiazolidines , azetidines , sulfonamides , benzamides , pyrrolidines , succinamic acids , acetamides , thieno(2,3-)pyridines , thieno(2,3-)-1,2,4-triazolo(1,5-)pyrimidines , thieno(2,3-) pyrimidines , and thieno(2,3-)pyridines derivatives incorporated into -substituted 3-indolylthiophenes were prepared by an initial reaction of 2-amino-4-(-substituted-1-indol-3-yl)thiophene-3-carbonitriles with different reagents. The antifungal activity of the newly synthesized compounds was evaluated against two strains of fungi, namely, (ATCC-10231) and (ATCC-10535). However, the mode of action of the most promising antifungal compounds was assessed by docking with cytochrome P450 14 α-sterol demethylase (CYP51) (PDB ID: 1EA1).
Results and conclusion
Compound showed good inhibitory activity against both (ATCC-10231) and (ATCC-10535), with minimum inhibitory concentrations values of 9 and 36 μg/disk, respectively, compared with fluconazole, with minimum inhibitory concentrations values of 8 and 34 μg/disk. Docking results showed that compound had the highest docking score, with a binding energy of −30.25 kJ/mol, which is in agreement with the experimental activity value.

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