Designed synthetic pathway of stereoselective novel monocyclic cis‐bis‐β‐lactams including a 1,3,4‐thiadiazole‐2,5‐dithiol constituent: Antimicrobial activity, molecular docking

Abstract

A simple synthetic method has been developed for novel monocyclic bisβ-lactams including a 1,3,4-thiadiazole-2,5-thiol constituent via [2 + 2] cycloaddition reactions, that is, Staudinger reaction (ketene-imine) of acyl chloride and numerous aromatic imines. Easily available starting materials, an easy workup, a simple purification process, no column chromatography needed, and a great yield are specific features of this work. Spectroscopic methods revealed the confirmation of synthesized products. Products were easily purified through a simple crystallization technique. The stereochemistry of bisβ-lactam derivatives at C-3 and C-4 stereocenters was validated by 1 H NMR spectra. All synthesized products exhibited good antimicrobial activities against three Gram-positive bacteria Staphylococcus aureus, Bacillus anthracis, and Clostridium perfringens, and two Gram-negative bacteria Escherichia coli, Brucella abortus. The molecular docking studies were carried out with the target receptor from E. coli, S. aureus, B. anthracis, B. abortus, and C. perfringens of PDB ID: 3T88, 4Q7G, 3Q2O, 4WJM, and 6PV4, respectively, to obtain a moderate binding interaction.

Synthesis, characterization, and biological activity using computational study of synthesized monocyclic β-lactam ligands

“…1. Introduction β-lactams are the well-known four membered heterocyclic amide found in a great number of biologically active compounds as well as naturally occurring antibiotics [1][2][3]. The effectiveness and absence of toxicity have made β-lactam containing organic compounds as one of the most successful antibiotics in history of mankind [4].…”