Synthesis, biological evaluation and molecular docking studies of quinoline‐conjugated 1,2,3‐triazole derivatives as antileishmanial agents

Abstract

In the present work, we have synthesized novel quinoline-conjugated 1,2,3-triazole derivatives 6a-l starting from substituted acetanilides in five steps. The synthesized compounds were screened for their antileishmanial activity. Quinoline-conjugated 1,2,3-triazole compounds 6c (IC 50 = 15.1 μg/ml), 6d (IC 50 = 14.6 μg/ml) and 6e (IC 50 = 14.3 μg/ml) displayed potent antileishmanial activity when compared with standard sodium stibogluconate (IC 50 = 14.3 ± 1.5 μg/ml). A molecular docking study against Leishmania major pteridine reductase (Lm-PTR1) suggests that these compounds have the potential to become lead molecules in antileishmanial drug discovery.

Evolution of the Quinoline Scaffold for the Treatment of Leishmaniasis: A Structural Perspective

“…Still, in 2021, another research group developed a series of twelve novel quinoline-1,2,3-triazole hybrids and evaluated them against L. donovani promastigotes, followed by molecular docking studies against L. major pteridine reductase ( Lm -PTR1) [ 67 ]. From their results, this research group was able to verify that three of the derivatives present significant levels of antileishmanial activity, with IC 50 values ranging from 29.55 µM to 31.05 µM, similar to the reference drug AmB.…”

“…One year later, in 2022, Sabt et al developed a series of twenty quinoline-isatin hybrids and evaluated them for their antileishmanial activity against both L. major promastigotes and amastigotes ( Figure 32 ) [ 67 ]. Considering their activity against promastigotes, the results demonstrated that all the evaluated derivatives present considerable levels of antileishmanial activity with IC 50 values ranging from 0.51 ± 0.06 µM to 5.95 ± 0.28 µM, being more active than the reference drug miltefosine (IC 50 = 7.90 ± 0.26 µM).…”

“…In terms of mechanism of action, based on the molecular docking studies, the authors suggest that this might be associated with their effect on the enzyme PTR1, since all the derivatives demonstrate a significant binding affinity to the enzyme, with the theoretical results following the same pattern as the experimental ones. One year later, in 2022, Sabt et al developed a series of twenty quinoline-isatin hybrids and evaluated them for their antileishmanial activity against both L. major promastigotes and amastigotes (Figure 32) [67]. Considering their activity against promastigotes, the results demonstrated that all the evaluated derivatives present considerable levels of antileishmanial activity with IC 50 values ranging from 0.51 ± 0.06 µM to 5.95 ± 0.28 µM, being more active than the reference drug miltefosine (IC 50 = 7.90 ± 0.26 µM).…”

5‐Arylidene‐2,4‐thiazolidinediones as Cysteine Protease Inhibitors against Leishmania Donovani

“…The most adopted approaches for developing anti‐leishmanial agents are target‐based drug discovery and the repurposing of drugs. In Leishmania spp , numerous molecular targets have been explored in diverse metabolic pathways, allowing the discovery of new drug candidates; some are in the advanced stages of development [8] . Therefore, searching for molecules with anti‐leishmanial activity is still needed.…”

“…In Leishmania spp, numerous molecular targets have been explored in diverse metabolic pathways, allowing the discovery of new drug candidates; some are in the advanced stages of development. [8] Therefore, searching for molecules with anti-leishmanial activity is still needed.…”