Lipophilicity and Pharmacokinetic Properties of New Anticancer Dipyridothiazine with 1,2,3-Triazole Substituents

Abstract

The lipophilicity parameters (logP_calcd, R_M0 and logP_TLC) of 10 new active anticancer dipirydothiazines with a 1,2,3-triazole ring were determined theoretically using computational methods and experimentally by reversed-phase TLC. Experimental lipophilicity was assessed using mobile phases (a mixture of TRIS buffer and acetone) using a linear correlation between the R_M retention parameter and the volume of acetone. The R_M0 parameter was correlated with the specific hydrophobic surface b, revealing two congenerative subgroups: 1,2,3-triazole-1,6-diazaphenothiazines and 1,2,3-triazole-1,8-diazaphenothiazines hybrids. The R_M0 parameter was converted into the logP_TLC lipophilicity parameter using a calibration curve. The investigated compounds appeared to be moderately lipophilic. Lipophilicity has been compared with molecular descriptors and ADME properties. The new derivatives followed Lipinski's, Ghose's and Veber's rules.

Keywords: 1,2,3-triazole; Lipinski’s, Ghose’s, Veber’s rules; RP-TLC, ADME properties; anticancer activity; dipyridothiazine; lipophilicity.