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

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.

Copper-Catalyzed One-Pot Synthesis of Thiazolidin-2-imines

“…The case of thiazolines, thiazolidinones, and thiazolidines is of particular interest, given that they have important biological applications against neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, as well as anticonvulsant, anti-inflammatory, anticancer, antiviral, antihypertensive, and antiparasitic properties, among others . Examples include etozoline A (Figure A), which exhibits antihypertensive activity, ralitoline B (Figure B), which exhibits anticonvulsant properties, 4-adamantyl-2-thiazolylimino-5-arylidene-4-thiazolidinones C (Figure C), which exhibit antibacterial activity, 3-thiazolidine-benzoic acid derivative D (Figure D), which exhibits anticancer activity, , specifically acting as a PPARγ antagonist, benzimidazo-thiazolinone-ylidine derivatives E (Figure E), which exhibit antifungal activity, and thiazolidine-ylidene derivative F (Figure F), which exhibits antibacterial activity against Salmonella enterica . When the carbonyl group in the five-membered thiazolidinone core of compound C , D , or F is replaced with carbon-based substituents, compounds with antiproliferative activity against breast cancer are obtained …”