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Current Topics in Medicinal Chemistry

Author(s): Lucianna Rabelo Pessoa de Siqueira, Larissa Pelágia de Lima Ferreira, Gevanio Bezerra de Oliveira Filho, Marcos Victor Gregório de Oliveira, Aline Ferreira Pinto, Vanessa Gouveia de Melo Silva, Paulo André Teixeira de Moraes Gomes, Marcos Veríssimo de Oliveira Cardoso, Maria de Nazaré Correia Soeiro, Flaviana Alves dos Santos, Maíra Galdino da Rocha Pitta, Janine Siqueira Nunes, Moacyr Jesus Barreto de Melo Rego and Ana Cristina Lima Leite*

DOI: 10.2174/1568026623666221226090807

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Synthesis, ADMET Prediction, and Antitumor Profile of Phenoxyhydrazine- 1,3-thiazoles Derivatives

Page: [265 - 282] Pages: 18

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Abstract

Background: Cancer is one of the most important barriers to increasing life expectancy in all countries in the 21st century. Investigations of new anti-cancer 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.

Methods: 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.

Results: Compound 2b induced cellular viability on MOLT-4 (37.1%), DU145 (41.5%), and HL- 60/MX1 (58.8%) cells. On MOLT-4 cells, compound 2b exhibited an IC50 of 8.03 μM, and against DU145 cells, an IC50 of 6.04μM. Besides, at IC50 and fold of IC50, 20% to 30% of dead cells were found, most due to necrosis/late apoptosis. Most compounds no showed cytotoxicity against fibroblast cells L929 at the concentrations tested. The compound did not alter the cell cycle of DU145 cells when compared to the negative control. Therefore, compound 2b stands out against DU145 and MOLT-4 cells.

Conclusion: 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 a starting point for developing new antineoplastic agents.

Graphical Abstract

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