Synthesis of thiazole-based-thiourea analogs: as anticancer, antiglycation and antioxidant agents, structure activity relationship analysis and docking study

This work reports the convenient approach for the synthesis of thiazole based thiourea derivatives (1-21) from 2-bromo-1-(4-fluorophenyl)thiazole-1-one and phenyl isothiocyanates. The scope and diversity were achieved from readily available phenyl isothiocyanates. This protocol involves an oxidative C-S bond formation. Moreover, hybrid thiazole based thiourea scaffolds (1-21) according to literature known protocol were screened in vitro for anticancer Potential against breast cancer, antiglycation and antioxidant inhibitory profile. All newly developed scaffolds were showed moderate to good inhibitory potentials ranging from 0.10 +/- 0.01 mu M to 11.40 +/- 0.20 mu M, 64.20 +/- 0.40 mu M to 385.10 +/- 1.70 mu M and 8.90 +/- 0.20 mu M to 39.20 +/- 0.50 mu M against anticancer, antiglycation and antioxidant respectively. Among the series, compounds 12 (IC50 = 0.10 +/- 0.01 mu M), 10 (IC50 = 64.20 +/- 0.40 mu M) and 12 (IC50 = 8.90 +/- 0.20 mu M) with flouro substitution at phenyl ring of thiourea were identified to be the most potent among the series having excellent anticancer, antiglycation and antioxidant potential. The structure of all the newly synthetics scaffolds were confirmed by using different types of spectroscopic techniques such as HREI-MS, H-1- and C-13-NMR spectroscopy. To find structure-activity relationship, molecular docking studies were carried out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data.Communicated by Ramaswamy H. Sarma

Automated summary

This work presents a convenient approach for synthesizing thiazole-based thiourea derivatives. The derivatives were obtained from the reaction between 2-bromo-1-(4-fluorophenyl)thiazole-1-one and phenyl isothiocyanates. The derivatives showed moderate to good inhibitory potentials against anticancer, antiglycation, and antioxidant, with compounds 12, 10, and 12 being the most potent among the series.