Synthesis and biological evaluation of 2-(5-substituted-1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)- N-substituted-hydrazinecarbothioamides
- Med Chem Res. 2013;22(4):2014-2022. doi: 10.1007/s00044-012-0184-x.
- 1. 1Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Rajajinagar, Bangalore, 560010 Karnataka India.
- 2. 2Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
Abstract: Various 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (4a, b) and 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-(phenyl-4-substituted)hydrazinecarbothioamide (5a-h) derivatives were synthesized. The compounds were screened for cytotoxicity against human HeLa and CEM T-lymphocytes as well as murine L1210 cells. The compounds were also screened for β-lactamase inhibitory activity, Antiviral, Antibacterial, and Antifungal activity against various strains of Microorganisms. Several of these compounds were endowed with low micromolar 50 %-cytostatic concentration (IC50) values, and some were virtually equally potent as melphalan. The most potent inhibitors against the murine leukemia cells (L1210) were also the most inhibitory against human T-lymphocyte (CEM) tumor cells. Derivative 2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazinecarbothioamide 5c emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed Antiviral activity against HEL cell cultures (IC50 11-20 μM). Moderate antimicrobial activity was observed for all derivatives. The encouraging cytostatic and Antiviral activity data provide an adequate rationale for further modification of these molecular scaffolds.
Graphical abstract: Derivative 5c (1.9-4.4 μM) emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed Antiviral activity against HEL cell cultures (IC50 11-20 μM).