title: Targeting Cancer Stem Cells with Novel 4-(4-Substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1H)-one/thiones.
abstract: Novel 4-(4-substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1H)-one/thione derivatives (DHP1-9) were designed, synthesized, characterized and evaluated for antitumor activity against cancer stem cells. The compounds were synthesized in one pot. EnaminonesE1andE2were reacted with substituted benzaldehydes and urea/thiourea in the presence of glacial acetic acid. The synthesized compounds were characterized by spectral analysis. The compounds were screened in vitro against colon cancer cell line (LOVO) colon cancer stem cells. Most of the compounds were found to be active against side population cancer stem cells with an inhibition of >50% at a 10 μM concentration. CompoundsDHP-1,DHP-7andDHP-9were found to be inactive. CompoundDHP-5exhibited an in vitro anti-proliferative effect and arrested cancer cells at the Gap 2 phase (G2) checkpoint and demonstrated an inhibitory effect on tumor growth for a LOVO xenograft in a nude mouse experiment.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. mabhat@ksu.edu.sa.
authors.forename: Mashooq Ahmad
authors.initials: MA
authors.lastname: Bhat
authors.affiliation: Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. harm101696@hotmail.com.|Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. harm101696@hotmail.com.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Dhfyan
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. malomar1@ksu.edu.sa.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Al-Omar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011743:Pyrimidines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013871:Thiones / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013871:Thiones
keywords: antitumor activity; cancer stem cells; dihydropyrimidine; enaminones