Highly divergent complexity molecules, having spirooxindole core structure, possess excellent bioactivities. The 1,3-dipolar cycloaddition reaction is one of the most efficient approach for the rapid synthesis of spirooxindole analogues. Herein, we report the synthesis of a series of spirooxindolone analogues via multicomponent reaction of chalcone, based on cyclohexanone, substituted isatin (isatin, 5-Cl-isatin, and 5-Br-isatin), and secondary amine of the amino acids (L-Proline and Thioproline). The included activities of the resulting spirooxazolines, including anti-inflammatory, anti-leishmanial, and cytotoxic activity against 3T3 and HeLa cell lines. Among series of nine diphenyl substituted derivatives of spiro fused benzylidine thioazol indolines (IVa-IVi), compounds IVb (IC 50 = 5.8 � 0.9 μM), IVc (IC 50 = 2.4 � 1.3 μM), IVd (IC 50 = 5.0 � 0.6 μM), and IVg (IC 50 = 10.4 � 4.6 μM) have shown potent anti-inflammatory activity, several fold more active than the standard drug, ibuprofen (IC 50 = 11.2 � 1.9 μM). Whereas, compounds IVa (IC 50 = 18.0 � 1.1 μM), and IVh (IC 50 = 26.0 � 3.4 μM) exhibited a significant anti-inflammatory potential. All other compounds (IVe and IVf) were found to be inactive. Two meta flouro substituted phenyl rings containing compound IVc (IC 50 = 2.4 � 1.3 μM) was the most potent member of the series. In order to rationalize the observed biological activities of the spirooxindole-pyrrolothiazole derivatives, in silico studies were also performed. The results of present study identify a new series of potent anti-inflammatory agents, deserve to be further investigated as leads.[a] G. Lotfy, Dr. Y. M. A. Aziz, Prof. M. M. Said have shown a significant anti-inflammatory potential. All other compounds (VId and VIe) were found to be inactive. Two ortho, meta dichloro substituted phenyl rings containing compound VIc (IC 50 = 4.2 � 1.8 μM) was found to be the most active Scheme 1. Synthesis of target thioazol/pyrrol indolines analogues IVa-i and VIa-h.