Antileishmanial Potential of Berberine Alkaloids From Berberis glaucocarpa Roots: Molecular Docking Suggests Relevant Leishmania Protein Targets

Abstract

Leishmaniases are a spectrum of poverty-linked neglected parasitic diseases that are endemic in 88 countries around the globe and affect millions of people every year. Currently available chemotherapeutic options are inadequate due to side effects, high cost, prolonged treatment, and parasite resistance. Thus, there is an existing need to develop new potent and safer leishmanicidal drugs. Considering the folkloric antiulcer and leishmanicidal use of the genus Berberis and its alkaloids, 5 reported alkaloids, namely berberine (1), palmatine (2), columbamine (3), 8-trichloromethyldihydroberberine (4), and jatrorrhizine (5), were isolated from the roots of Berberis glaucocarpa using classical (column and preparative chromatography) and modern isolation techniques (Sephadex LH-20). Their structures were elucidated and established from 1D and 2D spectroscopic data. The isolated alkaloids displayed excellent antileishmanial potential with IC50 values ranging from 1.50 to 2.56 µM: 1 (1.50 ± 0.53 µM), 2 (2.31 ± 0.37 µM), 3 (2.56 ± 0.48 µM), 4 (1.40 ± 0.90 µM), 5 (2.44 ± 1.34 µM). While the IC50 value for the standard drug (Amphotericin-B) was found to be 1.08 ± 0.95 µM. All of the isolated alkaloids displayed excellent antileishmanial potential as well as minimal cytotoxicity against THP-1 monocytic cells. Molecular docking analysis has revealed Leishmania N-myristoyl transferase, methionyl-tRNA synthetase, pteridine reductase 1, oligopeptidase B, tyrosyl-tRNA synthetase, and/or glycerol-3-phosphate dehydrogenase to be potential protein targets for the alkaloids.

Beneficial Effects of Natural Alkaloids from Berberis glaucocarpa as Antidiabetic Agents: An In Vitro, In Silico, and In Vivo Approach

“…Berberine ( WA1 ), palmatine ( WA2 ), and 8-trichloromethyl dihydroberberine ( WA3 ) used in this investigation were extracted from B. glaucocarpa Stapf, and the spectroscopic results agree with previously published literature . Streptozotocin, Tween-80, α-glucosidase, and substrate ( p -nitrophenyl-α- d -glucopyranoside) were bought from Sigma-Aldrich in Germany.…”

Potential for Aedes aegypti Larval Control and Environmental Friendliness of the Compounds Containing 2-Methyl-3,4-dihydroquinazolin-4-one Heterocycle

“…Molecular docking of the N -aryl-2-(2-methyl-4-oxoquinazolin-3(4 H )-yl)acetamide compounds was carried out according to Alamzeb et al. 31 The structures of the compounds were assembled using Spartan 18 for Windows, v 1.4.4 (Wavefunction, Inc.). Molecular docking was employed using Molegro Virtual Docker v 6.0.1 (Molegro ApS).…”

Identification of Potential Leishmania N-Myristoyltransferase Inhibitors from Withania somnifera (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation

“…Presently, the majority of research for the development of novel drugs focuses on this kind of analysis. Molecular docking has been employed in multiple studies to create new antiparasitic medications while considering a variety of targets to find new Leishmania treatments [ 8 ]. Discovering new leishmaniasis treatments is made more enticing by molecules implicated in parasite-specific metabolic processes [ 9 ].…”