title: Synthesis of N-substituted 5-iodouracils as antimicrobial and anticancer agents.
abstract: This study reports the synthesis of some substituted 5-iodouracils and their bioactivities. Alkylation of 5-iodouracils gave predominately N1-substituted-(R)-5-iodouracil compounds 7a-d (R = n-C(4)H(9), s-C(4)H(9), CH(2)C(6)H(11), CH(2)C(6)H(5)) together with N1,N3-disubstituted (R) analogs 8a-b (R = n-C(4)H(9), CH(2)C(6)H(11)). Their antimicrobial activity was tested against 27 strains of microorganisms using the agar dilution method. The analogs 7a, 7c and 7d displayed 25-50% inhibition against Branhamella catarrhalis, Neisseria mucosa and Streptococcus pyogenes at 0.128 mg/mL. No antimalarial activity was detected for any of the analogs when tested against Plasmodium falciparum (T9.94). Their anticancer activity was also examined. Cyclohexylmethyl analogs 7c and 8b inhibited the growth of HepG2 cells. Significantly, N1,N3-dicyclohexylmethyl analog 8b displayed the most potent anticancer activity, with an IC(50) of 16.5 microg/mL. These 5-iodouracil analogs represent a new group of anticancer and antibacterial agents with potential for development for medicinal applications.
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: Nirun
authors.initials: N
authors.lastname: Sornsongkhram
authors.forename: Ratchanok
authors.initials: R
authors.lastname: Pingaew
authors.forename: Apilak
authors.initials: A
authors.lastname: Worachartcheewan
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; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D001936:Moraxella catarrhalis / Q000187:drug effects; D042807:Neisseria mucosa / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D014498:Uracil; C048747:5-iodouracil
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