Dispirooxindole-pyrrolothiazoles: Synthesis, anti-cancer activity, molecular docking and green chemistry metrics evaluation

• Published in: Journal of molecular structure 2021-10, Vol.1242, p.130716, Article 130716
• Main Authors: Nivetha, Narayanasamy, Thangamani, Arumugam
• Format: Article
• Language: English
• Subjects: 1,3-dipolar cycloaddition; Anticancer activity; Azomethine ylide; Green chemistry metrics; Molecular docking; Spirooxindole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.130716

•A series of novel dispirooxindole-pyrrolothiazoles were synthesized in excellent yield.•These heterocyclic hybrids were achieved employing multicomponent reaction.•The reaction provided two new bonds, one new ring and four contiguous stereocenters.•Compound bearing benzyloxy group on the phenyl ring displayed potent activity.•The reaction demonstrates the higher environmental compatibility and sustainability. A modest library of a set of dispirooxindole-pyrrolothiazole derivatives 5a–n has been synthesized through multicomponent technique employing 1,3-dipolar cycloaddition reaction of azomethine ylide with novel dipolarophiles, 2,6-di (arylmethylidene) -4-methylcyclohexanones 4a–n without any catalyst. The reaction provides simple and efficient access to synthetically useful and biologically important dispirooxindole-pyrrolothiazoles in high yield (86–98%) with high degree of stereo-, regio-, and chemo-selectivities. All the synthesized compounds were characterized using popular spectral methods like IR, 1H NMR, 13C NMR and 2D NMR techniques. Further, the molecular structure of 5a was confirmed by single crystal XRD. The synthesized compounds were subjected to cytotoxicity evaluation using K562-leukemia cell line. Compound 5 k has been found to be an effective compound of this class in targeting K562-leukemia cell with IC50 value of 13.28 ± 0.11 µg/ml. From the molecular docking data, it is realized that these compounds 5a–n showed a binding energy between -8.1 and -10.8 kcal/mol and thereby inhibit Tyrosine Kinases. Smaller E-factor (0.13), high atom-economy (89.74%), percentage yield (98.00%), reaction mass efficiency (88.43%), and carbon efficiency (96.97%) are successful achieved for compound 5j. [Display omitted]