Synthesis of N-Substituted 5-Iodouracils as Antimicrobial and Anticancer Agents

Molecules

Supaluk Prachayasittikul¹  Nirun Sornsongkhram¹  Ratchanok Pingaew¹  Apilak Worachartcheewan¹  Somsak Ruchirawat¹ 

[1] ¹Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand ²Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand ³Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand

关键词: 5-iodouracil analogs;    N-alkylation;    antibacterial;    antimalarial;    anticancer activities;   

DOI  :  10.3390/molecules14082768

来源: mdpi

【 摘 要 】

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 mg/mL. These 5-iodouracil analogs represent a new group of anticancer and antibacterial agents with potential for development for medicinal applications.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.