Synthesis of N-substituted 5-iodouracils as antimicrobial and anticancer agents.
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.
Prachayasittikul
Supaluk
S
Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. supaluk@swu.ac.th
Sornsongkhram
Nirun
N
Pingaew
Ratchanok
R
Worachartcheewan
Apilak
A
Ruchirawat
Somsak
S
Prachayasittikul
Virapong
V
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
D000900:Anti-Bacterial Agents; D000962:Antimalarials; D014498:Uracil; C048747:5-iodouracil
Cancer Lett. 1998 Nov 27;133(2):169-75
10072166
Eur J Med Chem. 2009 Jun;44(6):2408-24
18992968
Eur J Med Chem. 2006 Sep;41(9):1093-101
16762461
J Parasitol. 1979 Jun;65(3):418-20
383936
Science. 1976 Aug 20;193(4254):673-5
781840
J Med Chem. 1992 Dec 11;35(25):4713-9
1469700
Bioorg Med Chem. 1997 Nov;5(11):2011-8
9416418
J Clin Virol. 2004 Jun;30(2):115-33
15125867
Acta Chem Scand. 1992 Jan;46(1):77-81
1599798
J Med Chem. 1976 May;19(5):639-42
1271405