One-Pot Synthesis of Novel 2-Imino-5-Arylidine-Thiazolidine Analogues and Evaluation of Their Anti-Proliferative Activity against MCF7 Breast Cancer Cell Line.

Marian N Aziz,Amany Iskander,Delphine Gout,Avisankar Chini,Arzoo Patel,Carl J Lovely,Subhrangsu S Mandal

doi:10.3390/molecules27030841

Abstract

An efficient surface-mediated synthetic method to facilitate access to a novel class of thiazolidines is described. The rationale behind the design of the targeted thiazolidines was to prepare stable thiazolidine analogues and evaluate their anti-proliferative activity against a breast cancer cell line (MCF7). Most of the synthesized analogues exhibited increased potency ranging from 2–15-fold higher compared to the standard reference, cisplatin. The most active thiazolidines contain a halogenated or electron withdrawing group attached to the N-phenyl ring of exocyclic 2-imino group. However, combination of the two substituents did not enhance the activity. The anti-proliferative activity was measured in terms of IC50 values using an MTT assay.

Highlights

Thiazolidines, five-membered nitrogen- and sulfur-containing ring compounds, are among the most eminent of heterocyclic classes due to their broad applications
The substitution of methylene at position 4 in thiazolidine ring blocks the aerobic oxidation to the corresponding thiazolidinone but still resulted in compounds unstable at room temperature
All the compounds were analyzed through spectroscopic analysis and the exact configuration of the thiazolidines was confirmed by X-ray single crystal characterization for one compound 5f as an example for the synthesized library

Summary

Introduction

Thiazolidines, five-membered nitrogen- and sulfur-containing ring compounds, are among the most eminent of heterocyclic classes due to their broad applications. Most of these derivatives contain 4-methoxy benzylidene derivatives and show good selectivity toward breast cancer cell lines. Thiazolidines exhibit a broad array of medicinal applications, which have inspired researchers to develop novel methodologies with the scope limited to aryl derivatives [31,32,33] and long reaction times [32,34] In addition to these promising methodologies, multi-step reactions, metal catalysis, ultrasonic irradiation, microwave conditions, and catalyst-free and solvent-free approaches have been described for the synthesis of various derivatives of thiazolidines [4]

Methods

Discussion

Conclusion