Comparative Anticancer Potentials of Taxifolin and Quercetin Methylated Derivatives against HCT-116 Cell Lines: Effects of O -Methylation on Taxifolin and Quercetin as Preliminary Natural Leads.

Autor: Mohammed HA; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia.; Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt., Almahmoud SA; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia., El-Ghaly EM; Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt., Khan FA; Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, 31441 Dammam, Saudi Arabia., Emwas AH; Core Laboratories, King Abdullah University of Science and Technology (KAUST), 23955-6900 Thuwal, Saudi Arabia., Jaremko M; Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900 , Saudi Arabia., Almulhim F; Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900 , Saudi Arabia., Khan RA; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia., Ragab EA; Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2022 Dec 07; Vol. 7 (50), pp. 46629-46639. Date of Electronic Publication: 2022 Dec 07 (Print Publication: 2022).
DOI: 10.1021/acsomega.2c05565
Abstrakt: Six flavonoids present in Pulicaria jaubertii , i.e., 7,3'-di- O -methyltaxifolin ( 1 ), 3'- O -methyltaxifolin ( 2 ), 7- O -methyltaxifolin ( 3 ), taxifolin ( 4 ), 3- O -methylquercetin ( 5 ), and quercetin ( 6 ), were tested for their anticancer activities. The methylated flavonoids, compounds 1 - 3 and 5 , were evaluated for their anticancer activities in comparison to the non-methylated parent flavonoids taxifolin ( 4 ) and quercetin ( 6 ). The structures of the known compounds were reconfirmed by spectral analyses using 1 H and 13 C NMR data comparisons and HRMS spectrometry. The anticancer activity of these compounds was evaluated in colon cancer, HCT-116, and noncancerous, HEK-293, cell lines using the MTT antiproliferative assays. The caspase-3 and caspase-9 expressions and DAPI (4', 6-diamidino-2-phenylindole) staining assays were used to evaluate the apoptotic activity. All the compounds exhibited antiproliferative activity against the HCT-116 cell line with IC 50 values at 33 ± 1.25, 36 ± 2.25, 34 ± 2.15, 32 ± 2.35, 34 ± 2.65, and 36 ± 1.95 μg/mL for compounds 1 to 6 , respectively. All the compounds produced a significant reduction in HCT-116 cell line proliferation, except compounds 2 and 6 . The viability of the HEK-293 normal cells was found to be significantly higher than the viability of the cancerous cells at all of the tested concentrations, thus suggesting that all the compounds have better inhibitory activity on the cancer cell line. Apoptotic features such as chromatin condensation and nuclear shrinkage were also induced by the compounds. The expression of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after 48 h of treatment, suggesting cell death by the apoptotic pathways. The molecular docking studies showed favorable binding affinity against different pro- and antiapoptotic proteins by these compounds. The docking scores were minimum as compared to the caspase-9, caspase-3, Bcl-xl, and JAK2.
Competing Interests: The authors declare no competing financial interest.
(© 2022 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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