Synthesis and biological evaluation of 2-(5-substituted-1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-substituted-hydrazinecarbothioamides

Medicinal Chemistry Research
2013.0

Abstract

<h4>Abstract</h4>Various 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (<b>4a</b>, <b>b</b>) and 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-<i>N</i>-(phenyl-4-substituted)hydrazinecarbothioamide (<b>5a</b>-<b>h</b>) 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 (IC<sub>50</sub>) 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)-<i>N</i>-(4-methoxyphenyl)hydrazinecarbothioamide <b>5c</b> emerged as the most potent cytostatic compound among the tested compounds. Derivatives <b>4b</b>, <b>5a</b>, <b>5b</b>, and <b>5d</b> showed antiviral activity against HEL cell cultures (IC<sub>50</sub> 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.<h4>Graphical abstract</h4>Derivative <b>5c</b> (1.9-4.4 μM) emerged as the most potent cytostatic compound among the tested compounds. Derivatives <b>4b</b>, <b>5a</b>, <b>5b</b>, and <b>5d</b> showed antiviral activity against HEL cell cultures (IC<sub>50</sub> 11-20 μM).

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