ORIGINAL ARTICLE
Year : 2014  |  Volume : 13  |  Issue : 2  |  Page : 71-86

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


1 Department of Chemistry Natural Compounds, National Research Centre, Giza, Egypt
2 Department of Pharmacognosy, National Research Centre, Giza, Egypt

Correspondence Address:
Heba M Abo-Salem
Department of Chemistry Natural Compounds, National Research Centre, Giza
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-4315.147064

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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 4a-c , morpholinyl-acetamides 6a-c , 4-methylpiperazinylacetamides 7a-c , thiazolidines 10a-c , azetidines 12a-c - 13a-c , sulfonamides 14a-c - 15a-c , benzamides 16a-c , pyrrolidines 17a-c , succinamic acids 18a-c , acetamides 19a-c , thieno(2,3-c)pyridines 20a-c , thieno(2,3-e)-1,2,4-triazolo(1,5-c)pyrimidines 23a-c , thieno(2,3-d) pyrimidines 24a-c - 26a-c , and thieno(2,3-b)pyridines 27a-c derivatives incorporated into N-substituted 3-indolylthiophenes were prepared by an initial reaction of 2-amino-4-(N-substituted-1H-indol-3-yl)thiophene-3-carbonitriles 1a-c with different reagents. The antifungal activity of the newly synthesized compounds was evaluated against two strains of fungi, namely, Candida albicans (ATCC-10231) and Aspergillus niger (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 4a showed good inhibitory activity against both C. albicans (ATCC-10231) and A. niger ( 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 4a 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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