Synthesis of thiazolidine-2,4-dione derivatives: anticancer, antimicrobial and DNA cleavage studies.

In the search of efficient anticancer agents, here, new 5-(4-alkylbenzyledene)thiazolidine-2,4-dione derivatives (5a-g) have been successfully synthesized and characterized and are evaluated for anticancer and antimicrobial activities using DNA cleavage studies. In vitro studies on anticancer activity of compound 5d (NSC: 768619/1) was done against the full panel of 60 human tumor cell lines. The five-level dose activity results revealed that, the compound 5d was active against all the cell lines, it has shown potential activity against leukemia SR (GI50: 2.04 µM), non-small cell lung cancer NCI-H522 (GI50: 1.36 µM), colon cancer COLO 205 (GI50: 1.64 µM), CNS cancer SF-539 (GI50: 1.87 µM), melanoma SK-MEL-2 (GI50: 1.64 µM), ovarian cancer OVCAR-3 (GI50: 1.87 µM), renal cancer RXF 393 (GI50: 1.15 µM), prostate cancer PC-3 (GI50: 1.90 µM), and breast cancer MDA-MB-468(GI50: 1.11 µM). DNA cleavage studies revealed that at 50 µg/mL concentration, partial DNA digestion was observed and when the concentration is increasing to threefold (150 µg/mL), complete linear DNA digestion and partial supercoiled DNA digestion was observed. Further antimicrobial studies indicate that all the synthesized compounds except compound 5a possess prominent activity against all the screened microbial species. This study throws a ray of light in the field of anticancer drugs.

Photochemical synthesis and anticancer activity of barbituric acid, thiobarbituric acid, thiosemicarbazide, and isoniazid linked to 2-phenyl indole derivatives.

2-Phenyl-1H-indole-3-carbaldehyde-based barbituric acid, thiobarbituric acid, thiosemicarbazide, isoniazid, and malononitrile derivatives were synthesized under photochemical conditions. The antitumor activities of the synthesized compounds were evaluated on three different human cancer cell lines representing prostate cancer cell line DU145, Dwivedi (DWD) cancer cell lines, and breast cancer cell line MCF7. All the screened compounds possessed moderate anticancer activity, and out of all the screened compounds, 5-{1[2-(4-chloro-phenyl)2-oxo-ethyl]-2-phenyl-1H-indole-3-ylmethylene}-2-thioxo-dihydro-pyrimidine-4,6-dione (2b) and 5-{1[2-(4-methoxy-phenyl)2-oxo-ethyl]-2-phenyl-1H-indole-3-ylmethylene}-2-thioxo-dihydro-pyrimidine-4,6-dione (2d) exhibited marked antitumor activity against used cell lines. Additionally, barbituric acid derivatives were selective to inhibit cell line DWD and breast cancer cell lines.