QSAR of Antiproliferative Activity of N‐Substituted 2‐Amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles in Various Human Cancer Cells

Antiproliferative activities in vitro against some human cancer cell lines of N ‐substituted 2‐amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles were correlated with their structure‐dependent properties. Phase affinity: lipophilicity and phospholipophilicity were determined by Reversed‐Phase Overpressured Layer Chromatography (RP‐8 OPLC) and Immobilized Artificial Membrane (IAM) High‐Performance Liquid Chromatography (HPLC), respectively. Electronic and steric descriptors were calculated by computational methods. The results indicate that phospholipophilicity and electronic properties expressed by partial charge of atoms of 2‐amino‐1,3,4‐thiadiazole moiety are the main factors that influence the antiproliferative effects of studied compounds. The Quantitative Structure–Activity Relationship (QSAR) equations obtained by the Multiple Linear Regression (MLR) analysis predict activity of compounds of high and average effects precisely and can be used in screening of new potential antiproliferative analogues of 2‐amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazole set. At the same time, these dependences as well as Quantitative Activity–Activity Relationship (QAAR) equations point to some differences in the individual human cancer cell lines studied.