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Synthesis, In Vitro Evaluation, and Molecular Docking Studies of Azetidinones and Thiazolidinones of 2‐Amino‐5‐cyclopropyl‐1,3,4‐thiadiazole as Antibacterial Agents
Author(s) -
Patel Harun,
Mishra Lishu,
Noolvi Malleshappa,
Karpoormath Rajshekhar,
Singh Cameotra Swaranjit
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201400140
Subject(s) - lipinski's rule of five , chemistry , adme , bacillus subtilis , antibacterial activity , combinatorial chemistry , stereochemistry , escherichia coli , docking (animal) , polar surface area , antimicrobial , in vitro , in silico , molecule , biochemistry , organic chemistry , bacteria , biology , gene , medicine , genetics , nursing
In an attempt to find a new class of antimicrobial agents, a series of novel azetidin‐2‐ones 3a – e and thiazolidin‐4‐ones 4a – e of 2‐amino‐5‐cyclopropyl‐1,3,4‐thiadiazole were synthesized. The synthesized compounds were confirmed by melting point, IR, 1 H NMR, 13 C NMR, and mass spectroscopy. The β‐lactam derivative ( 3e ) was found to be the most potent compound of the series displaying excellent antibacterial activities against Staphylococcus aureus , Bacillus subtilis , Escherichia coli , and Pseudomonas aeruginosa with MIC values of 15.60, 31.50, 62.50, and 125 µg/mL, respectively, as compared to the positive control drug ampicillin. Molecular docking studies and determination of the leakage of UV 260 ‐ and UV 280 ‐absorbing material (nucleic acid material and protein) confirmed that the synthesized compounds inhibit cell wall synthesis by inhibiting PTB (transpeptidase enzyme). Lipinski's rule and in silico ADME pharmacokinetic parameters are within the acceptable range defined for human use, thereby indicating their potential as a drug‐like molecules.