Synthesis of phenylthiourea-based pyrazole, thiazole and/or pyran compounds: molecular modeling and biological activity

Abstract

The significant biological activity of phenylthiourea derivatives prompted the synthesis of a new phenylthiourea-based heterocyclic ring systems (pyrazole, thiazole, and pyran), and their chemical structures were elucidated by spectral data. The DFT/B3LYP methodology was applied to explore the configuration and energetic features of the FMO’s of the compounds. The derivatives exhibited comparable energy gap, ranging from 2.13 to 2.56 eV, and were arranged in the following order: 5 < 8 < 7 < 6 < 4b < 4a. The antitumor activity of the new phenylthiourea-based derivatives was investigated against diverse cell lines, such as HepG2, HCT-116, MCF-7, PC3, and WI38, using Doxorubicin as a reference drug. The hybrids 5, 6, and 8 revealed strong cytotoxic against HCT-116 (IC50 = 2.29 ± 0.46-9.71 ± 0.34 µM). Furthermore, the molecular docking studies of the compounds indicated that the hybrids 5, 6 and 8 exhibited the greatest docking score values, in accordance to the antitumor activity.