Anti-leishmanial physalins-Phytochemical investigation, in vitro evaluation against clinical and MIL-resistant L. tropica strains and in silico studies.

Cutaneous leishmaniasis (CL) is a major health problem in over 98 countries of the world, including Pakistan. The current treatments are associated with a number of adverse effects and availability problem of drugs. Therefore, there is an urgent need of easily available and cost effective treatments of CL- in Pakistan. The bioassay-guided fractionation and purification of crude extract of Physalis minima has led to the isolation of a new aminophysalin B (1), and eight known physalins, physalin B (2), 5ß,6ß-epoxyphysalin B (3), 5α-ethoxy-6ß-hydroxy-5,6-dihydrophysalin B (4), physalin H (5), 5ß,6ß-epoxyphysalin C (6), and physalin G (7), K (8), and D (9). It is worth noting that compound 1 is the second member of aminophysalin series, whereas compound 6 was fully characterized for the first time. The structures of compounds 1-9 were elucidated by spectroscopic techniques Whereas, the structural assignments of compounds 1 and 8 were also supported by single-crystal X-ray diffraction studies. The anti-leishmanial activity of isolated physlains 1-9 was evaluated against Leishmania major and Leishmania tropica promastigotes. Compounds 2, 3, and 5-7 (IC50 = 9.59 ± 0.27-23.76 ± 1.10 μM) showed several-fold more potent activity against L. tropca than tested drug miltefosine (IC50 = 42.75 ± 1.03 μm) and pentamidine (IC50 = 27.20 ± 0.01 μM). Whereas compounds 2, 3 and 5 (IC50 = 3.04 ± 1.12-3.76 ± 0.85 μM) were found to be potent anti-leishmanial agents against L. major, several fold more active than tested standard miltefosine (IC50 = 25.55 ± 1.03 μM) and pentamidine (IC50 = 27.20 ± 0.015 μM). Compounds 4 (IC50 = 74.65 ± 0.81 μM) and 7 (IC50 = 39.44 ± 0.65 μM) also showed potent anti-leishmanial ativity against the miltefosine-unresponsive L. tropica strain (MIL resistant) (miltefosine IC50 = 169.55 ± 0.78 μM). Molecular docking and predictive binding studies indicated that these inhibitors may act via targeting important enzymes of various metabolic pathways of the parasites.

Informations de copyright

Copyright: © 2022 Bano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.