Synthesis, ADMET prediction, and antitumor profile of phenoxy-hydrazine-1,3-thiazoles derivatives



The synthesis and antitumor activity of phenoxy-hydrazine-1,3-thiazoles derivatives



Cancer is one of the most important barriers to increasing life expectancy in every country of the world in the 21st century. The investigations of new anticancer drugs with low side effects are an urgent demand for medicinal chemists.



Considering the known antitumor and immunomodulatory activity of thiazoles, this work presents the synthesis and antineoplastic activity of new thiazoles.



The 22 new compounds (2a-v) were synthesized from different thiosemicarbazones and 2-bromoacetophenone. The compounds were evaluated on: MOLT-4, HL-60, HL-60/MX1, MM1S, SKMEL-28, DU145, MCF-7, and T47d.



Compound 2b induced cellular viability of less than 59% on MOLT-4, DU145, and HL-60/MX1 cells. On MOLT-4 cells, compound 2b exhibited an IC50 of 8.03 μM, and against DU145 cells an IC50 of 6.04 μM. Besides, at IC50 and fold of IC50, 20% to 30% of dead cells were found, most of which were due to necrosis/late apoptosis. Most parts of the compounds showed no cytotoxicity against fibroblast cells L929 at concentrations up to 400 μM. The compound does not appear to significantly influence the cell cycle by using IC50 and twice IC50 values. Therefore, compound 2b stands out against DU145 and MOLT-4 cells.



Our study reinforced the importance of 1,3-thiazoles nuclei in antitumor activity. In addition, derivative 2b stands out against DU145 and MOLT-4 cells and could be used as a starting point for the development of new antineoplastic agents.



1,3-Thiazoles; Bioisosterism; Cancer; DU145; MOLT-4; Antitumor.
