Microwave Assisted Synthesis, Characterization of Some New Isatin and Thiophene Derivatives as Cytotoxic and Chemopreventive Agents

Kiran      Gangarapu; Sarangapani      Manda; Sreekanth      Thota; Rajeshwar      Yerra; Subhas      S. Karki; Jan      Balzarini; Erik      De Clercq; Harukuni      Tokuda

doi:10.2174/1570180811209050934

Abstract

In obtaining some new cytotoxic and chemopreventive agents with potent antiproliferative activity against cancer cells, a series of new β-isatin aldehyde-N,N’-thiocarbohydrazone, bis-β-isatin thiocarbohydrazones, bis-β-isatin carbohydrazones, N,2-bis(thiophen-2-ylmethylidene) thiocarbohydrazone and N,2-bis(thiophen-2-ylmethylidene) carbohydrazone derivatives was synthesized by microwave oriented reaction and evaluated for their in vitro cytotoxic activity. The newly synthesized compounds were characterized based on spectral (FT-IR, NMR, MS) analyses. The inhibitory effects of synthesized compounds on the proliferation of murine leukemia cells (L1210), human T-lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) were assayed by using MTT assay. The compounds were also tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-Otetradecanoylphorbol- 13-acetate (TPA). In vitro evaluation of these schiff bases revealed mild to moderate cytotoxic activity in a dose dependent manner. The results of the in vitro inhibitory activities of synthetic compounds against EBVEA activation with IC50 ranges from 485-535 (mol ratio/32pmol/TPA). Chlorine group containing derivatives did not show increased inhibitory activity against tumor promoter TPA induction. Sulphur containing derivatives also did not show a high inhibitory potency in this system.

Keywords: Carbohydrazide, Cytotoxic activity, Epstein-Barr virus antigen (EBV-EA) activation, Isatin, Thiophene-2- carboxaldehyde, Thiocarbohydrazide, Isatin–β-thiosemicarbazone derivatives, antihistamine, Cancer chemoprevention