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

Author:

Leite Ana Cristina Lima1ORCID,de Siqueira Lucianna Rabelo Pessoa12ORCID,de Lima Ferreira Larissa Pelágia12ORCID,de Oliveira Filho Gevanio Bezerra1ORCID,de Oliveira Marcos Victor Gregório1ORCID,Pinto Aline Ferreira1ORCID,de Melo Silva Vanessa Gouveia1ORCID,de Moraes Gomes Paulo André Teixeira1ORCID,de Oliveira Cardoso Marcos Veríssimo3ORCID,de Nazaré Correia Soeiro Maria4ORCID,dos Santos Flaviana Alves2ORCID,da Rocha Pitta Maíra Galdino2ORCID,Nunes Janine Siqueira1ORCID,de Melo Rego Moacyr Jesus Barreto2ORCID

Affiliation:

1. Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-520, Recife, PE, Brazil

2. Therapeutic Innovation Research Center, Federal University of Pernambuco, Recife, Pernambuco, Brazil

3. Laboratory of Prospection of Bioactive Molecules, University of Pernambuco, 56328-903, Petrolina, PE, Brazil

4. Laboratory of Cell Biology, Institute Oswaldo Cruz, Fiocruz, Av. Brasil 4365, 21040-900, Rio de Janeiro, Brazil

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 immunomodulato-ry activity of thiazoles, this work presents the synthesis and antineoplastic activity of new thiazoles. Method: 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. Result: 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 fibro-blast 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.

Funder

Fundação de Amparo à Ciência e Tecnologia de Pernambuco

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery,General Medicine

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