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Synthesis, Chemotherapeutic Screening and Docking Studies of NSAID Inserted Peptide‐Triazole Hybrid Molecules
Author(s) -
Srinivas Suryapeta,
Neeraja Papigani,
Naveen Kuntala,
Banothu Venkanna,
Dubey Pramod K.,
Mukkanti Khagga,
Pal Sarbani
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202000492
Subject(s) - autodock , docking (animal) , chemistry , mtt assay , triazole , antibacterial activity , stereochemistry , antimicrobial , cytotoxicity , peptide , combinatorial chemistry , dna gyrase , bacteria , biochemistry , escherichia coli , organic chemistry , biology , in vitro , medicine , genetics , nursing , in silico , gene
A series of peptide based new tryptophan‐1,2,3‐triazole‐naproxen derivatives were explored as prospective antibacterial / cytotoxic agents. These derivatives were prepared via a multi‐step method involving CuAAC as a key step and characterized by spectral data. The synthesized derivatives were evaluated for their antimicrobial activities against one Gram‐positive ( S. aureus ) and three Gram‐negative ( E. coli, K. pneumoniae and P. vulgaris ) bacteria using an agar‐well diffusion protocol where amoxycillin was used as a reference compound. Most of these compounds showed antibacterial activities when tested at 0.4 mg / 50 μl concentration. Compound 9 e i. e. N ‐(1‐amino‐1‐oxo‐3‐phenylpropan‐2‐yl)‐3‐(1‐((1‐(2‐((2‐chlorophenyl)amino)‐2‐oxoethyl)‐1 H ‐1,2,3‐triazol‐4‐yl)methyl)‐1 H ‐indol‐3‐yl)‐2‐(2‐(6‐methoxynaphthalen‐2‐yl)propanamido)propanamide exhibited good activities against all the strains. The potential DNA gyrase inhibitory activity of this compound was investigated by molecular docking studies carried out using Autodock Vina software. Compound 9 e showed an impressive ΔG bind of −10.0 kcal/mol. The cytotoxicity of the obtained compounds was also assessed against A549 cancer cell line (human lung carcinoma) by an MTT assay. Several of these compounds showed promising activity while 9 e showed lowest IC 50 value. A brief SAR for both antibacterial / cytotoxic activities of compounds tested is presented. Overall, compound 9 e has emerged as an initial hit molecule for further study.