Cytotoxic 2‐(2′‐Hydroxyphenyl)benzothiazolylquinoline Analogues and their In Vitro Screening through Developmental Assays†

Abstract

AbstractXenobiotics good pharmacodynamic effect should be evaluated with acceptable drug like properties during the drug discovery process. Benzothiazolyl‐quinoline derivatives are with reported biological and anticancer activity. In the present study, compounds were screened for potency determination in Caco‐2 (Human Epithelial Colorectal Adenocarcinoma) cell line and the most potent compound was evaluated through some of the drug development assays. Experimental protocols were set for stability and solubility (in buffer pH 7.4), metabolic stability, metabolite profiling, Caco‐2 permeability, P‐gp (P‐glycoprotein) inhibition in MDCK (Madin‐Darbey Canine Kidney)‐MDR1 overexpressed cells and CYP induction study by using LC‐MS/MS(Liquid Chromatography Tandem Mass spectrometry) method. The compound was stable and soluble in buffer pH 7.4, less permeable across Caco‐2 cell monolayer, unstable in microsomes, inhibitor of efflux P‐gp transporter and an inducer CYP (Cytochrome P450) 1 A2. The most potent compound (i. e. 6 k) was with high solubility, low permeability and high CLint (intrinsic clearance) in liver microsomes. Therefore it was preliminary classified as class III compound as per biopharmaceutics classification system (BCS) and Class I compound as per biopharmaceutical drug disposition classification system (BDDCS).