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-C4H9, s-C4H9, CH2C6H11, CH2C6H5) together with N1,N3-disubstituted (R) analogs 8a-b (R = n-C4H9, CH2C6H11). 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 IC50 of 16.5 μg/mL. These 5-iodouracil analogs represent a new group of anticancer and antibacterial agents with potential for development for medicinal applications.
Highlights
A number of pyrimidine bases have been shown to possess antiviral and anticancer activities [1], uracils possessing halogens at the 5-position e.g. 5-fluorouracil; a well known anticancer drug [2], and its N1-substituted derivative 1 [3], as well as nucleoside analogs 2 and 3 of 5-iodouracil and 5-trifluoromethyluracil, which are antivirals [4]
We report the synthesis of analogs 5 and 6 and their evaluation for antibacterial, antimalarial and anticancer actions
It was found that alkylation of 5-iodouracil with RBr took place predominately at the N1 position when R was derived from a primary or secondary alkyl bromide to give the products 1-(1-butyl)-5iodopyrimidine-2,4(1H, 3H)-dione (7a, R = n-C4H9, 28%), 1-(2-butyl)-5-iodopyrimidine-2,4(1H, 3H)dione (7b, R = s-C4H9, 6.1%), 1-(cyclohexylmethyl)-5-iodopyrimidine-2,4(1H, 3H)-dione
Summary
A number of pyrimidine bases have been shown to possess antiviral and anticancer activities [1], uracils possessing halogens at the 5-position e.g. 5-fluorouracil; a well known anticancer drug [2], and its N1-substituted derivative 1 [3], as well as nucleoside analogs 2 and 3 of 5-iodouracil and 5-trifluoromethyluracil, which are antivirals [4]. The mass spectra of analogs 7a-d and 8a-b all exhibited their molecular ions and base peaks resulting from fragmentations of alkyl or aralkyl at the N1- and/or Antibacterial activity of the analogs 1-(1-butyl)-5-iodopyrimidine-2,4(1H, 3H)-dione (7a), 1-(cyclohexylmethyl)-5-iodopyrimidine-2,4(1H,3H)-dione (7c) and 1-benzyl-5-iodopyrimidine-2,4(1H,3H)dione (7d) and 1,3-bis(cyclohexylmethyl)-5-iodopyrimidine-2,4(1H, 3H)-dione (8b) compounds and was evaluated against 27 strains of microorganisms using the agar dilution method [15].
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