Three compounds related to ribavirin inhibited IMPDH and had weak to moderate antiviral activity. Cytotoxicity adversely affected the antiviral selectivity of ETCAR. As with ribavirin, reduction in intracellular GTP may play a role in virus inhibition.
A series of 5’-O-[N-(salicyl)sulfamoyl]-2-aryl-8-aza-3-deazaadenosines were designed to block mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) through inhibition of the essential adenylating enzyme MbtA. The synthesis of the 2-aryl-8-aza-3-deazaadenosine nucleosides featured sequential copper-free palladium-catalyzed Sonogashira coupling of a precursor 4-cyano-5-iodo-1,2,3-triazolonucleoside with terminal alkynes and Minakawa-Matsuda annulation reaction. These modified nucleosides were shown to inhibit MbtA with apparent Ki values ranging from 6.1 to 25 nM and to inhibit Mtb growth under iron-deficient conditions with minimum inhibitory concentrations ranging from 12.5 to >50 μM.
Human
African Trypanosomiasis caused by Trypanosoma brucei species is one of the most damaging neglected tropical diseases.
While the number of newly diagnosed cases per year is record low,
there is still high interest in the development of new antitrypanosomal
agents in case of resistance to currently used drugs and their combinations,
and to replace drugs with serious side effects. We report a series
of 7-methyl-7-deazapurine (5-methyl-pyrrolo[2,3-d]pyrimidine) ribonucleosides bearing alkyl, methylsulfanyl, methylamino,
or diverse alkoxy groups at position 6 that was prepared through glycosylation
of 6-chloro-7-methyl-7-deazapurine followed by nucleophilic substitutions
or cross-coupling reactions at position 6 and deprotection. Most of
the title nucleosides displayed significant activity against Trypanosoma brucei brucei and T. b. gambiense at submicromolar or nanomolar concentrations and low cytotoxicity
and thus represent promising candidates for further development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.