Evaluation of electronic, lipophilic and membrane affinity effects on antiproliferative activity of 5-substituted-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles against various human cancer cells

The QSAR studies of 5-substituted-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles set of antiproliferative activity against human cancer cell lines have been performed. Electronic properties of compounds were estimated by the Hartree–Fock method at 6-31G** level. Lipophilicity and membrane affinity parameters were determined by the chromatographic methods RP-8 OPLC and IAM HPLC, respectively. Mono- and multivariable regression analyses were performed. The principle factor for determination of activity of compounds is partial charge of nitrogen (qN3, qN4) and carbon (qC5) atoms of the 1,3,4-thiadiazole ring. Biological effect is also connected with molar refractivity (CMR) and lipophilicity of derivatives obtained by RP-8 chromatography. The analysis of the QSAR equations for individual cell lines indicates both similarities and differences of electron, steric factors and hydrophobic–hydrophilic character of the analogues of the tested set affecting the antiproliferative activity.

Graphical abstractThe QSAR studies of 5-substituted 2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles against four human cancer cell lines are presented. The partial charge of nitrogen (qN3, qN4) and carbon (qC5) atoms of 1,3,4-thiadiazole ring, molecular refractivity and lipophilicity provide valuable information and have a significant role in the assessment of the antiproliferative activity of compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide