Novel diastereoselective synthesis of spiropyrrolidine-oxindole derivatives as anti-breast cancer agents

Abstract

A novel class of diastereoselective spiropyrrolidine-oxindole derivatives were synthesized from isatin, 2-phenylthiazolidine-4-carboxylic acid and chalcone in a one-pot multicomponent reaction via 1,3-dipolar cycloaddition. The advantages of this methodology are the mild reaction conditions, high diastereoselectivity and high yield. These derivatives exhibited promising anti-cancer activity against the human breast cancer cell lines.

The application of isatin-based multicomponent-reactions in the quest for new bioactive and druglike molecules

“…The synthetic approach consisted of a 1,3-dipolar cycloaddition reaction of azomethine ylides, generated in situ from isatin and proline derivatives, to activated dipolarophiles, which was also applied by other groups to get access to similar spiropyrrolidine-oxindole derivatives with some structural differences in the framework, depending on the dipolarophile used. For instance, the group of Kumar used chalcone derivatives (a,b-unsaturated ketones) as dipolarophiles in a similar 3-MCR approach to get a family of diastereoselective spiropyrrolidine-oxindole system (Scheme 1B) [53]. Using acetic acid as catalyst, the reaction proceeded smoothly under mild conditions (18 examples e 60e80% yield).…”

Synthesis of spiro-fused heterocyclic scaffolds through multicomponent reactions involving isatin

“…81 These derivatives exhibited promising anti-cancer activity against the human breast cancer cell lines. …”

An expeditious and environmentally benign synthesis of dispiro-3-phenylpyrrolothiazoles in ACI/EG eutectic mixture and its antioxidant and antimicrobial activities against urinary tract pathogens

“…Having medicinal values, thiazolidine ring systems play an important role in organic synthesis particularly antimicrobial substances such as penicillins, cephalosporins, narcodicins, thienamicyn and other compounds that have physiological activities have been prepared from thiazolidine [8]. It is noted that spiropyrrolothiazole analogues are interesting because of their wide range of biological activities such as anti-cancer [9], anti-diabetic [10], antibiotic [11], anti-inflammatory [12], hepatoprotective [13], anti-convulsant [14], anti-leukemic agents [15], Alzheimer disease [16], and also good in anti-mycobacterial [17]. Spiro indolin-2-one nucleus was reported to treat diabetic patients, HIV-1 protease inhibitors, potent gastrain/CCK-B receptor antagonist and for growth hormone secretagogue receptor agonists [18].…”