Discovery of 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea as a promising anticancer drug via synthesis, characterization, biological screening, and computational studies.

Autor: Mohammed YHI; Department of Biochemistry, Faculty of Applied Science, University of Hajjah, Hajjah, Yemen. issayasser16@gmail.com.; Department of Pharmacy, Faculty of Medicine and Medical Science, University of Al-Razi, Sana'a, Yemen. issayasser16@gmail.com., Shamkh IM; Botany and Microbiology Department, Faculty of Science, Cairo University, Giza, Egypt.; Chemo and Bioinformatics Lab, Bio Search Research Institution (BSRI), Giza, Egypt., Alharthi NS; Department of Medical Laboratory Sciences, College of Applied Medical Sciences in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia., Shanawaz MA; Department of Public Health, Faculty of Applied Medical Sciences, Albaha University, Albaha, 65431, Saudi Arabia., Alzahrani HA; Department of Basic Sciences, Faculty of Applied Medical Sciences, Albaha University, Albaha, 65431, Saudi Arabia., Jabbar B; Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, 53700, Pakistan., Beigh S; Department of Public Health, Faculty of Applied Medical Sciences, Albaha University, Albaha, 65431, Saudi Arabia., Alghamdi S; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia., Alsakhen N; Department of Chemistry, Faculty of Science, The Hashemite University, Zarqa, Jordan., Khidir EB; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia., Alhuthali HM; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia., Karamalla THE; Faculty of Medicine, Helwan University, Helwan, Cairo, Egypt., Rabie AM; Head of Drug Discovery and Clinical Research Department, Dikernis General Hospital (DGH), Magliss El-Madina Street, Dikernis City 35744, Dikernis, Dakahlia Governorate, Egypt. amgadpharmacist1@yahoo.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Dec 20; Vol. 13 (1), pp. 22824. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1038/s41598-023-44662-x
Abstrakt: Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using flow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC 50  = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored - 9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and - 7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.
(© 2023. The Author(s).)
Databáze: MEDLINE
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