Abstract

Fawzia Z. El-Ablack*, Mayada A. El-Zakzouk and Faten Z. mohamed

ABSTRACT

In trying to develop new anticancer agents, 5,7-diamino-6-(benzo[d]thiazol-2-yl)-3-phenylthiazolo[4,5-b] pyridine-2(3H)-thione derivative was designed, synthesized. The design was based on a molecular hybridization approach, and evaluated in-vitro for their anti-proliferative activity against human hepatocellular carcinoma cell line HePG-2, human breast adenocarcinoma MCF-7, colorectal carcinoma HCT-116, and Human prostate cancer PC-3 cell lines using a colorimetric MTT assay. Additionally, the synthesized compounds are also tested for their in vitro antioxidant activity by DPPH methods in which compounds exhibited good antioxidant activity. The calf thymus DNA binding activity of enaminonitrile thiazole compound and benzo[d]thiazol-2-yl pyridine derivative were studied by UV-Vis absorption titration and viscosity measurements also molecular docking of the tested compounds was carried out to investigate the DNA binding affinity of the tested compound with the prospective target, DNA (PDB-: 1BNA;6BNA).The results suggest that these compounds bind to DNA in an intercalative mode and the intrinsic binding constants (Kb) of diamino-benzo[d]thiazol-2-yl-thiazoe-and enaminonitrile thiazole with CT-DNA were found to be (7.24×105 and 5.59×105 M-1 ) . The antimicrobial activities of thiazole derivative were tested against gram negative bacteria (Escherichia coli, Klebsilla pneumonia and Pseudomonas sp), gram positive bacteria (Staphylococcus aureus, Bacillus cereus) and fungal (Aspergillus niger, Fusarium oxysporum and Candida albicans). Docking calculations were carried out using Docking Server (Bikadi, Hazai, 2009). Besides, the docking results for synthesized derivatives were in agreement with the in vitro antitumor results.