Version 1
: Received: 22 December 2022 / Approved: 23 December 2022 / Online: 23 December 2022 (10:23:38 CET)
Version 2
: Received: 25 December 2022 / Approved: 26 December 2022 / Online: 26 December 2022 (06:39:44 CET)
How to cite:
Sharma, H.; Sehgal, R.; Shekhar, N.; Kaur, U.; Medhi, B. Antiparasitic effect of Farnesol against Leishmania major: a rationale from in vitro and in silico investigations. Preprints2022, 2022120458. https://doi.org/10.20944/preprints202212.0458.v2
Sharma, H.; Sehgal, R.; Shekhar, N.; Kaur, U.; Medhi, B. Antiparasitic effect of Farnesol against Leishmania major: a rationale from in vitro and in silico investigations. Preprints 2022, 2022120458. https://doi.org/10.20944/preprints202212.0458.v2
Sharma, H.; Sehgal, R.; Shekhar, N.; Kaur, U.; Medhi, B. Antiparasitic effect of Farnesol against Leishmania major: a rationale from in vitro and in silico investigations. Preprints2022, 2022120458. https://doi.org/10.20944/preprints202212.0458.v2
APA Style
Sharma, H., Sehgal, R., Shekhar, N., Kaur, U., & Medhi, B. (2022). Antiparasitic effect of Farnesol against <em>Leishmania major</em>: a rationale from <em>in vitro</em> and <em>in silico</em> investigations. Preprints. https://doi.org/10.20944/preprints202212.0458.v2
Chicago/Turabian Style
Sharma, H., Upninder Kaur and Bikash Medhi. 2022 "Antiparasitic effect of Farnesol against <em>Leishmania major</em>: a rationale from <em>in vitro</em> and <em>in silico</em> investigations" Preprints. https://doi.org/10.20944/preprints202212.0458.v2
Abstract
Leishmaniasis is a vector-borne parasitic infection caused by the bite of female Phlebotomine sandflies. World Health Organization (WHO) estimates 100,000 cases to be reported annually on a global scale, moreover, 13 million people were infected between 2010 and 2015 worldwide. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic Cutaneous leishmaniasis. The cytotoxic effect of Farnesol against L. major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L. major was evaluated by flow cytometry. In the findings, Promastigotes were reduced at 167 µM/mL & the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Farnesol at 172 µM/ml. In addition, Farnesol demonstrated no cytotoxicity on macrophages as the IC50 value was 945 µM/ml; it induced significant apoptosis dose-dependent on L. major promastigotes. In silico protein-ligand binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potentials of Farnesol alone and in combination with other conventional drugs using clinical settings.
Keywords
Leishmania major; Sesquiterpene; in silico; in vitro; Flow Cytometry
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Commenter: Rakesh Sehgal
Commenter's Conflict of Interests: Author