Biological evaluation and pharmacokinetic profiling of a coumarin-benzothiazole hybrid as a new scaffold for human gliomas

Abstract

A coumarin-benzothiazole hybrid 3 was recently reported as a potential anticancer lead compound based on antioxidant and α-glucosidase inhibitory activities. Herein, we report anticancer activity of the lead compound 3 at a single dose (10 μM) against a panel of 60 cancer cell lines. Analysis of the five-dose screening by NCI against 60 cancer cell lines is discussed as well. Investigation of the pharmacokinetic properties of the lead compound is presented in this study. The effect of the hybrid compound 3 on the viability of various human glioma cells and its ability to cross the blood brain barrier (BBB) in PAMPA-BBB assay were further investigated. The oxidative alterations caused by 3 in human glioma cells were determined using colorimetric measurements. In vitro and in vivo pharmacokinetic profiling of 3 support its potential as a candidate for further screening in animal models of gliomas. The drug likeness properties of 3 were further investigated by in silico assessment of its physicochemical properties and toxicity risks. Moreover, in silico studies were conducted for evaluation of ADMET of 3. The selective and potent anticancer activity of 3 as well as desirable pharmacokinetic properties renders 3 a promising lead for development of anticancer therapeutics.

Keywords

• Anticancer activity
• Pharmacokinetic
• ADMET
• In silico
• Hybridization