Synthesis and antiproliferative activity of 2-oxo-3-phenylquinoxaline derivatives and related compounds against colon cancer.

Autor:	Gomaa MS; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University P. O. Box 1982 Dammam 31441 Eastern Province Kingdom of Saudi Arabia., Ahmed AHA; Chemistry Department, Faculty of Medicinal Science, University of Science and Technology Aden 15201 Yemen., El Rayes SM; Department of Chemistry, Faculty of Science, Suez Canal University Ismailia Egypt samir_elrayes@science.suez.edu.eg., Ali IAI; Department of Chemistry, Faculty of Science, Suez Canal University Ismailia Egypt samir_elrayes@science.suez.edu.eg., Fathalla W; Department of Physical Sciences, Faculty of Engineering, Suez Canal University Ismailia Egypt., Alturki MS; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University P. O. Box 1982 Dammam 31441 Eastern Province Kingdom of Saudi Arabia., Al Khzem AH; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University P. O. Box 1982 Dammam 31441 Eastern Province Kingdom of Saudi Arabia., Almalki AH; Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University P. O. Box 11099 Taif 21944 Saudi Arabia.; Addiction and Neuroscience Research Unit, College of Pharmacy, Taif University Al-Hawiah Taif 21944 Saudi Arabia., Aldawsari MF; Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University Al-kharj 11942 Saudi Arabia., Pottoo FH; Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Eastern Province P. O. Box 1982 Dammam 31441 Saudi Arabia., Khan FA; Department of Stem Cell Biology, Institute for Research & Medical Consultations, (IRMC), Imam Abdul Rahman Bin Faisal University Dammam 31441 Saudi Arabia., Amir M; Department of Natural Products, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University Dammam 1982 Saudi Arabia.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2024 Nov 08; Vol. 14 (48), pp. 35679-35695. Date of Electronic Publication: 2024 Nov 08 (Print Publication: 2024).
DOI:	10.1039/d4ra06822j
Abstrakt:	We have designed 17 new 2-oxo-3-phenylquinoxalines via the chemoselective Michael reaction of 3-phenylquinoxalin-2(1 H )-one with acrylic acid derivatives. The ester, ethyl 3-(2-oxo-3-phenylquinoxalin-1(2 H )-yl)propanoate, was reacted with hydroxylamine and hydrazine to produce N -hydroxy-3-(2-oxo-3-phenylquinoxalin-1(2 H )-yl)propanamide and hydrazide, respectively. Further modifications were made through reactions with isothiocyanates and azide coupling with amines, yielding thiosemicarbazides and N -alkyl derivatives. Molecular docking studies identified compound 7j as the most potent binder, fitting well into the active site, with the phenyl ring occupying the S1 pocket and the amino acid chain positioned in the S2 pocket. The synthesized compounds (2a, 4, 7a, 7g, 7d, 7h, 7e, 7b, 7c, 7f, and 7j) were evaluated for their anti-cancer activity on colorectal cancer (HCT-116) cells. Compounds 2a and 7j showed significant reductions in cell viability, with IC50 values of 28.85 ± 3.26 μg mL -1 and 26.75 ± 3.50 μg mL -1 , respectively. Image analysis of HCT-116 cells treated with 60 μg mL -1 of compound 7j for 48 hours revealed notable morphological changes in both nuclei and cells. The number of cells reduced from 447 in the control to 238 in the treated group, with a corresponding reduction in the area covered by cells from 41.9% to 17.6%. Nuclear disintegration and chromatin fragmentation were observed, confirming apoptosis. These results highlight the potent cytotoxic effect of compound 7j. Competing Interests: The authors declare that they have no competing interests. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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