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

Molecules

卷:27

Beata Morak-Młodawska¹  Małgorzata Jeleń¹ 

[1] Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland;

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

DOI  :  10.3390/molecules27041253

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown