title: Synthesis and structure-activity relationship of 2-thiopyrimidine-4-one analogs as antimicrobial and anticancer agents.
abstract: Considering that some thiopyrimidines were previously reported as potential therapeutics, the present study achieved novel analogs of bioactive 2-substituted thiopyrimidines-4-(3H)-ones via base catalyzed alkylation reaction of 2-thiouracil using alkyl and aralkyl bromides. The title compounds were 2-(1-butylthio)pyrimidine-4(3H)-one (5a), 2-(2-butylthio)pyrimidine-4(3H)-one (5b), 2-(cyclohexylmethylthio)pyrimidine-4(3H)-one (5c), 2-(benzylthio)pyrimidine-4(3H)-one (5d) and 2-(1-adamantylthio)pyrimidine-4(3H)-one (5e). Bioactivity tests revealed that thiopyrimidines 5a, 5c, 5d and 5e exhibited antimicrobial activity. The thiopyrimidine-4-one (5c) showed complete inhibition against Streptococcus pyogenes and Branhamella catarrhalis as well as antifungal action against Candida albicans. Significantly, the 1-adamantylthiopyrimidine (5e) was shown to be the most potent cytotoxic compound against multidrug-resistant small cell lung cancer (H69AR). Their structure-activity relationships were discussed.
authors.affiliation: Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. supaluk@swu.ac.th
authors.forename: Supaluk
authors.initials: S
authors.lastname: Prachayasittikul
authors.forename: Apilak
authors.initials: A
authors.lastname: Worachartcheewan
authors.forename: Chanin
authors.initials: C
authors.lastname: Nantasenamat
authors.forename: Maneekarn
authors.initials: M
authors.lastname: Chinworrungsee
authors.forename: Nirun
authors.initials: N
authors.lastname: Sornsongkhram
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
authors.forename: Virapong
authors.initials: V
authors.lastname: Prachayasittikul
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D001936:Moraxella catarrhalis / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C558539:2-thiopyrimidine-4-one; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000962:Antimalarials; D000970:Antineoplastic Agents; D011744:Pyrimidinones