Synthesis of Some Novel Semicarbazone and Thiosemicarbazone Derivatives of Isatin as Possible Biologically Active Agents

Aims: The development of new beneficial agents is one of the crucial aims in medicinal chemistry. Isatin is considered as a vital class of bioactive compounds exhibiting different biological activities. A series of nine new Semicarbazone (12a-i) and six new Thiosemicarbazone (14a-c, 14f-h) derivatives of isatin were prepared.

Methods: Synthesis of the desired compounds was done in two steps. In the first step, we alkylated the isatin ring by using different alkyl halides in DMF and in the presence of Ca2H. In the second step, the alkylated isatin was reacted with semicarbazide or thiosemicarbazide in ethanol and amount of acetic acid. Chemical structures of all the products were confirmed by IRi, ¹H NMRii, 13C NMR, and elemental analysis. The cytotoxic activities of the compounds were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) method against MCF-7iii and MDA-231iv breast cancer cell lines. Antimicrobial activities of these compounds against different species of microorganisms including Gram positive and Gram negative bacteria as well as fungi were also determined by broth micro-dilution method as recommended by CLSI (Clinical and Laboratory Standard Institute).

Results: Some of our compounds showed moderate cytotoxic activity but showed notable antibacterial and antifungal effects.

Conclusion: Replacement of aminophenyl benzothiazole with isatin had reduced the antimicrobial activities of the compounds. Maybe a complex of our synthesized compounds with some metals could be used to improve their antimicrobial activities.

i Infrared.

ii Nuclear Magnetic Resonance.

iii Michigan Cancer Foundation-7.

iv Mammary Drive Adenocarcinoma.