Thiazolyl-isatin derivatives: Synthesis, in silico studies, in vitro biological profile against breast cancer cells, mRNA expression, P-gp modulation, and interactions of Akt2 and VIM proteins.

Autor: Freitas LAB; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil., Sousa C; Pharmacological and Regulatory Sciences Group (PharmRegSci), Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia da Universidade de Lisboa, Lisbon, Portugal., Lima BS; Pharmacological and Regulatory Sciences Group (PharmRegSci), Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia da Universidade de Lisboa, Lisbon, Portugal., Duarte D; Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008, Lisboa, Portugal., Gomes PATM; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil., Ramos CGC; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil., Costa VCM; Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil., Pitta MGDR; Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil., Rêgo MJBM; Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil., de Simone CA; Departamento de Física e Informática, Instituto de Física de São Carlos, Universidade de São Paulo, 13560-970, São Carlos, SP, Brazil., Videira M; Pharmacological and Regulatory Sciences Group (PharmRegSci), Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia da Universidade de Lisboa, Lisbon, Portugal., Leite ACL; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil. Electronic address: ana.lleite@ufpe.br.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 May 01; Vol. 394, pp. 110954. Date of Electronic Publication: 2024 Mar 20.
DOI: 10.1016/j.cbi.2024.110954
Abstrakt: The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC). The activity profile on membrane proteins involved in chemoresistance and tumorigenic signaling proteins was also evaluated. Among the compounds tested, the compounds 4c and 4a stood out with IC 50 values of 1.23 and 1.39 μM, respectively, against the MDA-MB-231 cell line. Both compounds exhibited IC 50 values of 0.45 μM for the MCF-7 cell line. Compounds 4a and 4c significantly decreased P-gp mRNA expression levels in MCF-7, 4 and 2 folds respectively. Regarding the impact on tumorigenic signaling proteins, compound 4a inhibited Akt2 in MDA-MB-231 and compound 4c inhibited the mRNA expression of VIM in MCF-7.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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