Synthesis of novel spirooxindolo-pyrrolidines, pyrrolizidines, and pyrrolothiazoles via a regioselective three-component [3+2] cycloaddition and their preliminary antimicrobial evaluation

Abstract

A series of spirooxindolo-pyrrolidines, pyrrolizidines, and pyrrolothiazoles hybrid compounds were prepared in good yields by regioselective, three-component, 1,3-dipolar cycloaddition reactions between α, β-unsaturated ketones with furanyl substituents and unstable azomethine ylides, which were generated in situ from isatin and various types of amino acids. The synthesized compounds were screened for their antibacterial activities against a spectrum of pathogens. Preliminary studies identified compound 5c as a potent antimicrobial agent against drug-resistant bacteria. In addition, molecular docking studies indicated that compound 5c showed strong interactions with the active sites of lanosterol demethylase, dihydrofolate reductase, and topoisomerase II. This study provides an effective entry to the rapidly construction of a chemical library of heterocycles and compound 5c is one potent antibacterial lead for subsequent optimization.

Molecular diversity of spirooxindoles. Synthesis and biological activity

“…The synthesized compounds were screened for their antibacterial activities against a spectrum of pathogens [84].…”

Novel Hybrid Virtual Screening Protocol Based on Molecular Docking and Structure-Based Pharmacophore for Discovery of Methionyl-tRNA Synthetase Inhibitors as Antibacterial Agents

“…The 15 final hit compounds were purchased and screened for preliminary in vitro antibacterial activity against our five ATCC-bacterial strain panel ( Staphylococcus aureus ATCC 29213, Methicillin-resistant Staphylococcus aureus ATCC 43300, E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Klebsiella pneumoniae ATCC 700603) by using the standard broth dilution method [27,28]. As shown in Table 2, most compounds exhibited antibacterial activities with MIC (minimum inhibitory concentration) ranging from 4 to 64 μg/mL.…”

Regioselective Synthesis of Carbazole‐Grafted Dispirothiapyrrolizine Derivatives via 1,3‐Dipolar Cycloaddition Strategy

“…The spiro‐oxindolyl nucleus constitutes an integral part of many naturally occurring alkaloids, such as horsfiline, spiro tryprostatine A and B, elacomine, coerulescine, pteropodine, formosanine and alstonisine which have highly pronounced biological activities such as antimicrobial, inhibition of human NK‐1 receptor, potent non‐peptide inhibition of the p53–MDM2 interaction and aldose reductase inhibition . The potential use of thiapyrrolizine system in medicinal chemistry has been well recognized, enabling their use as anticancer, antimicrobial, antidiabetic, acetylcholinesterase‐ inhibition, and in treatment for Alzheimer disease …”