Unraveling the antitrypanosomal mechanism of benznidazole and related 2-nitroimidazoles: From prodrug activation to DNA damage was written by Dattani, Ambika;Drammeh, Isatou;Mahmood, Aishah;Rahman, Mahbubur;Szular, Joanna;Wilkinson, Shane R.. And the article was included in Molecular Microbiology in 2021.Application In Synthesis of 2-(2-Nitro-1H-imidazol-1-yl)acetic acid This article mentions the following:
Nitroheterocycles represent an important class of compound used to treat trypanosomiasis. They often function as prodrugs and can undergo type I nitroreductase (NTR1)-mediated activation before promoting their antiparasitic activities although the nature of these downstream effects has yet to be determined Here, we show that in an NTR1-dependent process, benznidazole promotes DNA damage in the nuclear genome of Trypanosoma brucei, providing the first direct link between activation of this prodrug and a downstream trypanocidal mechanism. Phenotypic and protein expression studies revealed that components of the trypanosome′s homologous recombination (HR) repair pathway (TbMRE11, γH2A, TbRAD51) cooperate to resolve the benznidazole-induced damage, indicating that the prodrug-induced lesions are most likely double stand DNA breaks, while the sequence/recruitment kinetics of these factors parallels that in other eukaryotes HR systems. When extended to other NTR1-activated 2-nitroimidazoles, some were shown to promote DNA damage. Intriguingly, the lesions induced by these required TbMRE11 and TbCSB activities to fix leading us to postulate that TbCSB may operate in systems other than the transcription-coupled nucleotide excision repair pathway. Understanding how existing trypanosomal drugs work will aid future drug design and help unlock novel reactions/pathways that could be exploited as targets for therapeutic intervention. In the experiment, the researchers used many compounds, for example, 2-(2-Nitro-1H-imidazol-1-yl)acetic acid (cas: 22813-32-7Application In Synthesis of 2-(2-Nitro-1H-imidazol-1-yl)acetic acid).
2-(2-Nitro-1H-imidazol-1-yl)acetic acid (cas: 22813-32-7) belongs to imidazole derivatives. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. Imidazole derivatives have antibacterial, antifungal and anticancer functionality. It interacts with DNA and also binds to protein and stops cell division.Application In Synthesis of 2-(2-Nitro-1H-imidazol-1-yl)acetic acid
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem