Evaluating the leishmanicidal activity of m-Nitrocinnamic acid containing lipophilic peptide against leishmania donovani

Chaitali Karmakar; Deblina Sarkar; Amaltas Ghosh; Debasish Haldar; Mitali Chatterjee

doi:10.1016/j.actatropica.2025.107703

Evaluating the leishmanicidal activity of m-Nitrocinnamic acid containing lipophilic peptide against leishmania donovani

Acta Trop. 2025 Jun 18:268:107703. doi: 10.1016/j.actatropica.2025.107703. Online ahead of print.

Authors

Chaitali Karmakar¹, Deblina Sarkar¹, Amaltas Ghosh¹, Debasish Haldar², Mitali Chatterjee³

Affiliations

¹ Department of Pharmacology, Institute of Post Graduate Medical Education and Research, 244 B, Acharya JC Bose Road, Kolkata 700020, India.
² Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia 741 246, India.
³ Department of Pharmacology, Institute of Post Graduate Medical Education and Research, 244 B, Acharya JC Bose Road, Kolkata 700020, India. Electronic address: ilatimc@gmail.com.

PMID: 40541897
DOI: 10.1016/j.actatropica.2025.107703

Abstract

Studies have demonstrated that m-Nitrocinnamic acid containing Lipophilic Peptide (LP) exhibits leishmanicidal activity against Leishmania major promastigotes; however, its efficacy against the amastigote form remains unclear. In this study, we evaluated the activity of LP against Leishmania donovani, the causative agent of Visceral Leishmaniasis (VL), wherein LP demonstrated both anti-promastigote and anti-amastigote activity, as measured by MTS cell viability assay and droplet digital PCR (ddPCR) respectively, the IC₅₀ derived being 22.0 and 6.0 µM respectively, while the CC₅₀ was >500 µM, which translated into a safety index >83. LP induced leishmanicidal activity by triggering a redox imbalance in promastigotes, by enhancing the generation of reactive oxygen species (ROS) and caused lipid peroxidation, but failed to impact on generation of mitochondrial superoxide. Furthermore, as N-acetyl cysteine (NAC) attenuated the parasiticidal properties of LP via scavenging the free radicals, it substantiated that the cytotoxicity of LP was mediated by inducing a redox imbalance. An apoptotic-like cell death was demonstrated in promastigotes, features being an enhanced annexin V positivity, altered mitochondrial membrane potential, and cell cycle arrest at sub G₀/G₁. Collectively, this study confirmed that LP exhibited leishmanicidal activity against L. donovani that was mediated by an apoptotic-like cell death via disruption of redox homeostasis, and could be considered as a compound worthy of further pharmacological consideration.

Keywords: Anti-leishmanial; Leishmania donovani; Lipophilic Peptide (LP); Redox imbalance; m-Nitrocinnamic acid.