Monocyclic Nitro-heteroaryl Nitrones with Dual Mechanism of Activation: Synthesis and Antileishmanial Activity.

ABSTRACT: 5-Nitro-furan nitrones (1) and 5-nitro-thiophene nitrones (2) were synthesized in one step. Compounds 1a-c had the most potent leishmanicidal activity against intracellular amastigote forms of Leishmania amazonensis and L. infantum (from 0.019 to 2.76 μM), with excellent selectivity (from 39 to 5673). The comparison of the leishmanicidal activity in promastigotes of wild type L. donovani with those overexpressing nitroreductases NRT1 or NRT2 shows that 1a,b are activated by both, which could slow the development of resistance. Their redox potential (E _redox) obtained by cyclic voltammetry (-0.67 and -0.62 V) shows that the reduction of the nitro group is modulated by the nitrone group. Oral administration of <

SUBMITTER: Pacheco JDS 

PROVIDER: S-EPMC8436238 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature