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Rational design and eco-friendly one-pot multicomponent synthesis of novel ethylidenehydrazineylthiazol-4(5H)-ones as potential apoptotic inducers targeting wild and mutant EGFR-TK in triple negative breast cancer.
Abbass, Eslam M; Al-Karmalawy, Ahmed A; Sharaky, Marwa; Khattab, Muhammad; Alzahrani, Abdullah Yahya Abdullah; Hassaballah, Aya I.
Afiliación
  • Abbass EM; Department of Chemistry, Faculty of Science, Ain Shams University, Abbassiya 11566, Cairo, Egypt.
  • Al-Karmalawy AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt. Electronic address: akarmalawy@horus.edu.eg.
  • Sharaky M; Cancer Biology Department, Pharmacology Unit, National Cancer Institute (NCI), Cairo University, Cairo, Egypt.
  • Khattab M; Office of Research, University of Western Australia, Perth, Australia; Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo, Egypt.
  • Alzahrani AYA; Department of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail Assir, Saudi Arabia.
  • Hassaballah AI; Department of Chemistry, Faculty of Science, Ain Shams University, Abbassiya 11566, Cairo, Egypt.
Bioorg Chem ; 142: 106936, 2024 01.
Article en En | MEDLINE | ID: mdl-37890211
ABSTRACT
A novel series of ethylidenehydrazineylthiazol-4(5H)-ones were synthesized using various eco-friendly one-pot multicomponent synthetic techniques. The anticancer activity of compounds (4a-m) was tested against 11 cancer cell lines. While the IC50 of all compounds was evaluated against the most sensitive cell lines (MDA-MB-468 and FaDu). Our SAR study pinpointed that compound 4a, having a phenyl substituent, exhibited a significant growth inhibition % against all cancer cell lines. The frontier anticancer candidates against the MDA-MB-468 were also examined against the wild EGFR (EGFR-WT) and mutant EGFR (EGFR-T790M) receptors. Most of the synthesized compounds exhibited a higher inhibitory potential against EGFR-T790M than the wild type of EGFR. Remarkably, compound 4k exhibited the highest inhibitory activity against both EGFR-WT and EGFR-T790M with IC50 values (0.051 and 0.021 µM), respectively. The pro-apoptotic protein markers (p53, BAX, caspase 3, caspase 6, caspase 8, and caspase 9) and the anti-apoptotic key marker (BCL-2) were also measured to propose a mechanism of action for the compound 4k as an apoptotic inducer for MDA-MB-468. Investigation of the cell cycle arrest potential of compound 4k was also conducted on MDA-MB-468 cancer cells. We also evaluated the inhibitory activities of compounds (4a-m) against both EGFR-WT and EGFR-T790M using two different molecular docking processes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas / Neoplasias Pulmonares / Antineoplásicos Límite: Humans Idioma: En Revista: Bioorg Chem Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas / Neoplasias Pulmonares / Antineoplásicos Límite: Humans Idioma: En Revista: Bioorg Chem Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Estados Unidos