Farhat Afrin ^1,2* Mohammad Islamuddin ^2,3,4 Wandayi Emmanuel Amlabu ^2,5,6 Garima Chouhan ^2,7* Ishaya Haruna Nock ^5,8* Dinkar Sahal ⁹ Hassan A. Hemeg ^10*

• ¹ Centre for Interdisciplinary Sciences, JIS University, JIS Institute of Advanced Studies and Research, Kolkata, Delhi, India
• ² Department of Biotechnology, Jamia Hamdard University, New Delhi, NCT of Delhi, India
• ³ Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, Louisiana, United States
• ⁴ Division of Comparative Pathology, Tulane National Primate Research Center, School of Medicine, Tulane University, Covington, Louisiana, United States
• ⁵ Department of Zoology, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna, Nigeria
• ⁶ West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana
• ⁷ Department of Biotechnology, Sharda University, Greater Noida, Uttar Pradesh, India
• ⁸ Nok University, Kaduna, Nigeria
• ⁹ International Centre for Genetic Engineering and Biotechnology (India), New Delhi, Delhi, India
• ¹⁰ Department of Clinical Laboratory Sciences, Taibah University, Medina, Al Madinah, Saudi Arabia

The incidence of leishmaniasis has escalated with the increase in drug resistant strains, toxicity of mainstay drugs, surfacing of the disease tentacles beyond the endemic zones and emergence as an opportunistic infection in HIV/AIDS and other life-threatening diseases. With negligible success in translation of pipeline vaccines, chemotherapy remains the sole arsenal in the fight against this neglected disease of poverty. Despite significant breakthroughs in high throughput drug discovery, there is an urgent need for quest of promising antileishmanials. Guiera senegalensis J. F. Gmel (Family: Combretaceae) leaves have the ethnobotanical claim of being used in the treatment of malaria and other related disease symptoms. Herein, we have studied the antileishmanial potential of the leaves of G. senegalensis and mechanistic effects of the bioactive fractions. The 70% crude methanolic extract and C-18 resin flash chromatography fractions were tested in vitro for antileishmanial activity against the promastigotes of Leishmania donovani (MHOM/IN/83/AG83). A 50% inhibitory concentration (IC50) of 6.2 µgml -1 and 3.47 µgml -1 for the 60% C-18 resin fraction against L. donovani promastigotes and amastigotes, respectively together with 50% cytotoxic concentration (CC50) of >500 µgml -1 against macrophage cell line and a 50% hemolytic concentration (HC50) of >100 µgml -1 against red blood cells (RBCs) indicate a high selectivity of this fraction against L. donovani promastigotes (83.3) and amastigotes (144.1). Gas chromatography-mass spectrometry (GC-MS) fingerprinting of the bioactive C-18 fraction revealed n-Hexadecanoic acid; beta-D-Glucopyranose, 1,6-anhydro-Dronabinol; Androst-5-en-3-ol, 4,4-dimethyl-(3 beta) as the major constituents. The antileishmanial activity was found to be mediated by apoptosis and necrosis. This is the first report of the antileishmanial activity of G. senegalensis, opening the possibilities of identifying novel pharmacophores against the Leishmania parasites.