Ureidopyrazine Derivatives: Synthesis and Biological Evaluation as Anti-Infectives and Abiotic Elicitors

Molecules

Pavlína Niklová¹  Ghada Bouz¹  Martin Juhás¹  Lenka Tůmová¹  Martin Doležal¹  Ondřej Janďourek¹  Jan Zitko¹  Zuzana Kovalíková¹  Pavla Paterová¹  Jiří Janoušek¹  Petr Kastner¹ 

[1] Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic;

关键词: abiotic elicitors;    anti-infectives;    callus culture;    ester;    Mycobacterium tuberculosis;    pyrazinoic acid;    ureidopyrazine;   

DOI  :  10.3390/molecules22101797

来源: DOAJ

【 摘 要 】

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become a frequently deadly infection due to increasing antimicrobial resistance. This serious issue has driven efforts worldwide to discover new drugs effective against Mtb. One research area is the synthesis and evaluation of pyrazinamide derivatives as potential anti-TB drugs. In this paper we report the synthesis and biological evaluations of a series of ureidopyrazines. Compounds were synthesized by reacting alkyl/aryl isocyanates with aminopyrazine or with propyl 5-aminopyrazine-2-carboxylate. Reactions were performed in pressurized vials using a CEM Discover microwave reactor with a focused field. Purity and chemical structures of products were assessed, and the final compounds were tested in vitro for their antimycobacterial, antibacterial, and antifungal activities. Propyl 5-(3-phenylureido)pyrazine-2-carboxylate (compound 4, MICMtb = 1.56 μg/mL, 5.19 μM) and propyl 5-(3-(4-methoxyphenyl)ureido)pyrazine-2-carboxylate (compound 6, MICMtb = 6.25 μg/mL, 18.91 μM) had high antimycobacterial activity against Mtb H37Rv with no in vitro cytotoxicity on HepG2 cell line. Therefore 4 and 6 are suitable for further structural modifications that might improve their biological activity and physicochemical properties. Based on the structural similarity to 1-(2-chloropyridin-4-yl)-3-phenylurea, a known plant growth regulator, two selected compounds were evaluated for similar activity as abiotic elicitors.

【 授权许可】

Unknown