Design, synthesis and mechanistic anticancer activity of new acetylated 5-aminosalicylate-thiazolinone hybrid derivatives.

Autor:	Ramadan WS; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates., Saber-Ayad MM; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.; College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates., Saleh E; Medical Biochemistry and Molecular Biology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 12613, Egypt., Abdu-Allah HHM; Faculty of Pharmacy, Assiut University, Assiut 16122, Egypt., El-Shorbagi AA; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.; Faculty of Pharmacy, Assiut University, Assiut 16122, Egypt., Menon V; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates., Tarazi H; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates., Semreen MH; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates., Soares NC; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates., Hafezi S; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates., Venkatakhalam T; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates., Ahmed S; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.; Department of Biosciences and Chemistry, College of Health, Wellbeing and Life sciences, University of Sheffield Hallam, Sheffield S1 1WB, United Kingdom., Kanie O; Department of Applied Biochemistry, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan., Hamoudi R; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.; College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.; Division of Surgery and Interventional Science, Faculty of Medical Science, University College London, London, United Kingdom., El-Awady R; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Dec 09; Vol. 27 (1), pp. 108659. Date of Electronic Publication: 2023 Dec 09 (Print Publication: 2024).
DOI:	10.1016/j.isci.2023.108659
Abstrakt:	The development of hybrid compounds has been widely considered as a promising strategy to circumvent the difficulties that emerge in cancer treatment. The well-established strategy of adding acetyl groups to certain drugs has been demonstrated to enhance their therapeutic efficacy. Based on our previous work, an approach of accommodating two chemical entities into a single structure was implemented to synthesize new acetylated hybrids ( HH32 and HH33 ) from 5-aminosalicylic acid and 4-thiazolinone derivatives. These acetylated hybrids showed potential anticancer activities and distinct metabolomic profile with antiproliferative properties. The in-silico molecular docking predicts a strong binding of HH32 and HH33 to cell cycle regulators, and transcriptomic analysis revealed DNA repair and cell cycle as the main targets of HH33 compounds. These findings were validated using in vitro models. In conclusion, the pleiotropic biological effects of HH32 and HH33 compounds on cancer cells demonstrated a new avenue to develop more potent cancer therapies. Competing Interests: The authors declare no competing interests. A patent application for the two compounds described in this article has been submitted. (© 2023 The Authors.)
Databáze:	MEDLINE
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