New multifunctional hybrids as modulators of apoptosis markers and topoisomerase II in breast cancer therapy: synthesis, characterization, and in vitro and in silico studies.

Autor: Alhamdi HW; College of Sciences, Biology Department, King Khalid University Abha 61413 Saudi Arabia., Alfaifi MY; King Khalid University, Faculty of Science, Biology Department Abha 9004 Saudi Arabia.; Tissue Culture and Cancer Biology Research Laboratory, King Khalid University Abha 9004 Saudi Arabia., Shati AA; King Khalid University, Faculty of Science, Biology Department Abha 9004 Saudi Arabia.; Tissue Culture and Cancer Biology Research Laboratory, King Khalid University Abha 9004 Saudi Arabia., Elbehairi SEI; King Khalid University, Faculty of Science, Biology Department Abha 9004 Saudi Arabia.; Tissue Culture and Cancer Biology Research Laboratory, King Khalid University Abha 9004 Saudi Arabia.; Cell Culture Lab, Egyptian Organization for Biological Products and Vaccines (VACSERA Holding Company) 51 Wezaret El-Zeraa St., Agouza Giza Egypt., Er-Rajy M; LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University Fez Morocco., Elshaarawy RFM; Department of Chemistry, Faculty of Science, Suez University 43533 Suez Egypt reda.elshaarawy@suezuniv.edu.eg., Hassan YA; Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology Gamasa Egypt., Zakrya R; Chemistry Department, Faculty of Science, Port-Said University Port-Said Egypt rzakrya@yahoo.com.
Jazyk: angličtina
Zdroj: RSC advances [RSC Adv] 2024 Sep 06; Vol. 14 (39), pp. 28555-28568. Date of Electronic Publication: 2024 Sep 06 (Print Publication: 2024).
DOI: 10.1039/d4ra04219k
Abstrakt: Recently, molecular hybrids of two or more active pharmacophores have shown promise for designing and synthesizing anticancer drugs. Herein, a new multifunctional hybrid (PAHMQ), combining azobenzene and quinoline pharmacophores, and its M(ii) complexes (MPAHMQ) have been successfully developed and structurally characterized. The MTT assay revealed CuBHTP as the most efficient and safe breast cancer treatment, with an IC 50 of 11.18 ± 0.39 μg mL -1 and a high selectivity index (SI) of 5.63 for cancer MCF-7 cells over healthy MCF10A cells. Moreover, the CuPAHMQ-treated MCF-7 cells experience a dramatic impact with regard to key apoptotic markers, including an increase in P53 and Bax expression, with a decrease in Bcl-2 expression levels compared to the untreated MCF-7 cells. Additionally, CuPAHMQ effectively halted the growth and division of MCF-7 cells by inducing cell cycle arrest in the crucial G1 and S phases, ultimately inhibiting both Topo II activity and cell proliferation. Molecular docking investigations validated the CuPAHMQ complex's groove binding and topoisomerase II binding, establishing it as a potent anticancer drug.
Competing Interests: The authors declare no conflict of interest.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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