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Synthesis, biological evaluation, and docking study of a series of 1,4‐disubstituted 1,2,3‐triazole derivatives with an indole‐triazole‐peptide conjugate
Author(s) -
Suryapeta Srinivas,
Papigani Neeraja,
Banothu Venkanna,
Dubey Pramod Kumar,
Mukkanti Khagga,
Pal Sarbani
Publication year - 2020
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.4020
Subject(s) - chemistry , autodock , click chemistry , docking (animal) , combinatorial chemistry , triazole , antibacterial activity , 1,2,3 triazole , stereochemistry , mtt assay , azide , dna gyrase , antimicrobial , conjugate , cycloaddition , indole test , escherichia coli , in silico , organic chemistry , bacteria , biochemistry , in vitro , medicine , mathematical analysis , genetics , nursing , mathematics , biology , gene , catalysis
A series of new compounds containing an indole‐triazole ‐ peptide conjugate were designed as potential agents possessing the dual anti‐bacterial and anticancer activities. Accordingly, 20 compounds were prepared via a multi‐step synthesis involving the copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) as a key step in moderate to high yield. All the synthesized compounds were purified by chromatographic techniques and characterized by IR, 1 H and 13 C NMR and mass spectral data. The synthesized derivatives were screened for their antimicrobial activities against one gram‐positive ( Staphylococcus aureus ) and three gram‐negative ( Escherichia coli , Klebsiella pneumonia , and Proteus vulgaris ) bacteria using an agar‐well diffusion method. Most of the compounds showed moderate to reasonable antibacterial activities especially the compound 9e that showed good activities against all the strains. The potential of DNA gyrase inhibitory activity of this compound was assessed by using molecular docking studies in silico carried out using Autodock Vina software. The low ΔG bind value (−9.4 Kcal/mol) of compound 9e suggested its good interactions with the target protein in silico. The cytotoxic activities of some of the compounds synthesized were evaluated via a MTT assay using the human lung cancer cell line A549. Several compounds showed promising activities among which compound 9b , 9k, and 9e showed low IC 50 values.