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Synthesis of Oxindole Analogues, Biological Activity, and In Silico Studies
Author(s) -
Lotfy Gehad,
Aziz Yasmine M. Abdel,
Said Mohamed M.,
El Ashry El Sayed H.,
El Tamany El Sayed H.,
Barakat Assem,
Ghabbour Hazem A.,
Yousuf Sammer,
UlHaq Zaheer,
Choudhary M. Iqbal
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201901228
Subject(s) - isatin , chemistry , chalcone , stereochemistry , hela , cycloaddition , oxindole , in silico , combinatorial chemistry , in vitro , organic chemistry , biochemistry , gene , catalysis
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 μ M), IVc (IC 50 =2.4±1.3 μ M), IVd (IC 50 =5.0±0.6 μ M), and IVg (IC 50 =10.4±4.6 μ M) have shown potent anti‐inflammatory activity, several fold more active than the standard drug, ibuprofen (IC 50 =11.2±1.9 μ M). Whereas, compounds IVa (IC 50 =18.0±1.1 μ M), and IVh (IC 50 =26.0±3.4 μ M) 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 μ M) 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.