{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T08:26:41Z","timestamp":1775636801110,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,23]],"date-time":"2021-05-23T00:00:00Z","timestamp":1621728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Researchers Supporting Project number (RSP-2020\/237), King Saud University, Riyadh, Kingdom of Saudi Arabia.","award":["Project number (RSP-2020\/237),"],"award-info":[{"award-number":["Project number (RSP-2020\/237),"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The pathogenesis of colorectal cancer is a multifactorial process. Dysbiosis and the overexpression of COX-2 and LDHA are important effectors in the initiation and development of the disease through chromosomal instability, PGE2 biosynthesis, and induction of the Warburg effect, respectively. Herein, we report the in vitro testing of some new quinoxalinone and quinazolinone Schiff\u2019s bases as: antibacterial, COX-2 and LDHA inhibitors, and anticolorectal agents on HCT-116 and LoVo cells. Moreover, molecular docking and SAR analyses were performed to identify the structural features contributing to the biological activities. Among the synthesized molecules, the most active cytotoxic agent, (6d) was also a COX-2 inhibitor. In silico ADMET studies predicted that (6d) would have high Caco-2 permeability, and %HIA (99.58%), with low BBB permeability, zero hepatotoxicity, and zero risk of sudden cardiac arrest, or mutagenicity. Further, (6d) is not a potential P-gp substrate, instead, it is a possible P-gpI and II inhibitor, therefore, it can prevent or reverse the multidrug resistance of the anticancer drugs. Collectively, (6d) can be considered as a promising lead suitable for further optimization to develop anti-CRC agents or glycoproteins inhibitors.<\/jats:p>","DOI":"10.3390\/molecules26113121","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:01:20Z","timestamp":1621814480000},"page":"3121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Synthesis and Characterization of Some New Quinoxalin-2(1H)one and 2-Methyl-3H-quinazolin-4-one Derivatives Targeting the Onset and Progression of CRC with SAR, Molecular Docking, and ADMET Analyses"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9771-8956","authenticated-orcid":false,"given":"Nahed","family":"El-Sayed","sequence":"first","affiliation":[{"name":"Egyptian Drug Authority (Formerly: National Organization for Drug Control and Research), 51 Wezaret El-Zerra St., Giza 35521, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taghreed","family":"Al-Otaibi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9430-7980","authenticated-orcid":false,"given":"Mona","family":"Alonazi","sequence":"additional","affiliation":[{"name":"Biochemistry Department, College of Sciences, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay","family":"Masand","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Vidya Bharati College, Camp, Amravati, Maharashtra 444 602, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-3201","authenticated-orcid":false,"given":"Assem","family":"Barakat","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"},{"name":"Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-2612","authenticated-orcid":false,"given":"Zainab","family":"Almarhoon","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-7483","authenticated-orcid":false,"given":"Abir","family":"Ben Bacha","sequence":"additional","affiliation":[{"name":"Biochemistry Department, College of Sciences, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"},{"name":"Laboratory of Plant Biotechnology Applied to Crop Improvement, Faculty of Science of Sfax, University of Sfax, Sfax 3038, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"977","DOI":"10.2147\/IJGM.S277272","article-title":"The incidence rate of colorectal cancer in Saudi Arabia: An observational descriptive epidemiological analysis","volume":"13","author":"Almatroudi","year":"2020","journal-title":"Int. J. Gen. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.mam.2019.05.001","article-title":"Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential","volume":"69","author":"Saus","year":"2019","journal-title":"Mol. 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