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2000
Volume 32, Issue 34
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Introduction

Leishmaniasis is an affliction caused by the protozoan parasites of the Leishmania genus. This disease impacts a substantial global populace, exceeding one million individuals, leading to disability-adjusted life years and fatalities, particularly within tropical regions. At present, the existing drug therapies have not attained a degree of efficacy that can be unequivocally classified as genuinely triumphant. In this context, the conception of novel compounds possessing the capacity to impede the parasite's life cycle at various stages holds considerable significance.

Methods

In this research endeavor, an exploration was undertaken involving the design and synthesis of nineteen derivatives incorporating the nitrovinyl pharmacophore. The subsequent evaluation of their impacts on was conducted through a combination of (amastigote and promastigote inhibition) and (molecular docking) investigations.

Results

All of the compounds were synthesized and purified with good yields. In the amastigote inhibition assay, compounds , , and showed better inhibitory effects than the standard drug meglumine antimonate (MA). Regarding the synergistic impact of synthesized compounds and MA together, all outcomes were significantly better than those of monotherapy of each in amastigote and macrophage forms. In the promastigote assay, compounds , , , , , , and demonstrated superior inhibitory effects compared to MA. Moreover, compounds , , and showed the best synergies with MA in inhibiting amastigotes. According to docking scores, 1XTP (a SAM-dependent methyltransferase) and 4G5D (Prostaglandin F synthase) receptors were found to be the most probable targets in their mechanism of action.

Conclusion

evaluations and computational analyses strongly suggest that these compounds could be effective against both amastigotes and promastigotes. Additionally, they exhibited notable synergistic interactions with MA against both living forms of the parasite.

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Targeting Leishmaniasis with Nitrovinyl Derivatives: Synthesis, In Vitro Assessment, and Computational Exploration
Curr. Med. Chem. 32, 7697 (2025); https://doi.org/10.2174/0109298673323271241002060614
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Supplements

Characterization and analytical data (FT-IR, 1H NMR, 13C NMR) related to all compounds have been reviewed in detail in a separate supplementary file. For this reason, only the analytical data of novel compounds (16 to 19) is introduced. Ortho-4-chloro benzyloxy-β-nitrostyrene 3153 (C-H), 2890 (C-H), 1625 (C=C), 1599 (C=C), 1507 & 1329 (NO), 1195 (C-O), 808 (C-Cl). 8.22 (1H, , =12Hz, CH), 7.85 (1H, , =15Hz, CH), 7.53-7.38 (6H, m, CH), 7.11-7.02 (2H, m, CH), 5.20 (2H, s, OCH). 158.2, 138.4, 135.2, 134.4, 134.3, 133.5, 132.3, 129.1, 128.8, 121.6, 119.5, 112.8, and 69.9. Para-4-chloro benzyloxy-β-nitrostyrene 3107 (C-H), 2941 & 2884 (C-H), 1630 (C=C), 1599 (C=C), 1493 & 1341 (NO), 1242 (C-O), 576 (C-Cl). 8.00 (1H, , =12Hz, CH), 7.56 (3H, brs, CH and CH), 7.40 (4H, brs, CH), 7.04 (2H, brs, CH), 5.13 (2H, s, OCH). 161.8, 138.9, 135.3, 134.5, 134.2, 131.2, 128.9, 128.8, 123, 115.8, and 69.5. Para-4-fluoro benzyloxy-β-nitrostyrene 3116 & 3042 (C-H), 2870 (C-H), 1604 (C=C), 1571 (C=C), 1512 & 1336 (NO), 1247 (C-O), 1172 (C-F). 8.00 (1H, , =15Hz, CH), 7.55 (1H, , =15Hz, CH), 7.54 (2H, , =9Hz, CH), 7.45 (1H, , =15Hz, CH), 7.13 (2H, t, =9Hz, CH), 7.05 (2H, d, =9Hz, CH), 5.12 (2H, s, OCH). 164.2, 161.9, 161.1, 138.9, 135.3, 131.8, 131.2, 129.5, 129.4, 122.9, 115.9, 115.8, 115.6, and 69.6. Para-4-methyl benzyloxy-β-nitrostyrene 3104 (C-H), 2935 (C-H), 1632 (C=C), 1603 (C=C), 1516 & 1352 (NO), 1253 (C-O). 8.00 (1H, , =12Hz, CH), 7.58-7.52 (3H, m, CH and CH), 7.36 (2H, , =9Hz CH), 7.26 (2H, , =9Hz, CH), 7.06 (2H, , =9Hz, CH), 5.15 (2H, s, OCH). 162.2, 139.1, 138.3, 135.1, 132.9, 131.2, 129.5, 127.7, 122.7, 115.8, 70.2, 21.2.

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  • Article Type:     Research Article
Keyword(s): amastigote; anti-leishmania; Leishmania major; molecular docking; Nitrovinyl; promastigote

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