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

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).

2,3-Dioxo-2,3-dihydroindole; Antimicrobial activity; Antiviral activity; Cytotoxicity assay; Thiosemicarbazones.