University of Khartoum

Isolation and Structure Elucidation of Leishmanicidal Alkaloids from Argemone mexicana L. and Nauclea latifolia Smith

Isolation and Structure Elucidation of Leishmanicidal Alkaloids from Argemone mexicana L. and Nauclea latifolia Smith

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Title: Isolation and Structure Elucidation of Leishmanicidal Alkaloids from Argemone mexicana L. and Nauclea latifolia Smith
Author: Mekki, Omima Mekki Khider
Abstract: Introduction: Leishmaniasis a group of clinical diseases affecting millions of the world populations in 88 countries. Accordingly, this disease is considered as one of the Neglected Tropical Diseases (NTDs) besides malaria, sleeping sickness, mycetoma and other fifteen NTDs. Chemotherapy for leishmaniasis is still deficient and there is an urgent need to discover novel antileishmanial agents, hence most of the currently available drugs have serious limitations such as long-term administration, unaffordable cost, toxicity, and developing resistance by these parasites. The objectives of this study is to isolate and elucidate the chemical structures of new anti-leishmanial secondary metabolites against both the promastigotes and amastigotes stages with special reference to alkaloids occurring in Argemone mexicana L. and Nauclea latifolia Smith, which are commonly growing plants in Sudan. Methods: The extraction of plant materials was followed by bioactivityguided fractionation using the promastigotes of L. donovani, L. major and L. tropica of the crude ethanolic extracts of A. mexicana and N. latifolia and their respective organic fractions as well as the water residue by colorimetric method. Isolation of pure compounds was achieved by high-performance liquid chromatography (HPLC). The isolated compounds were subjected to one- and two-dimensional Nuclear Magnetic Resonance (NMR) with special emphasis on 1D-NMR (1H, 13C, DEPT), 2D-NMR (COSY, HSQC, HMBC, NOESY) as well as UV, and mass spectrometry. Results: Bioactivity-guided fractionation revealed a remarkable difference in susceptibility of the three leishmania species. The crude ethanolic extract of A. mexicana exhibited the most prominent activity against the promastigotes of L. donovani (IC50 11.39 μg/mL) followed by the water residue (23.93 μg/mL) which is indicative of the hydrophilicity of the bioactive compounds.x The crude ethanolic extract and water residue of Nauclea latifolia exhibited weak activity against the promastigotes of L. donovani with IC50 of 46.86 and 30.45 μg/mL, respectively. Among the purified isolated alkaloids of Nauclea latifolia, strictosamide inhibited the proamastigotes of both L. major and L. tropica with IC50 of 77.67±1.11 and 80.40±3.00 μg/mL, respectively. The structurally related β- carboline alkaloid, naucleficine, however, showed no inhibition. Similarly, the isoquinoline alkaloid, norchelerythrine, isolated from A. mexicana, exhibited no leishmanicidal activity against L. major and L. tropica. Attempting computational chemistry by docking of the isolated compounds against 14 leishmanicidal targets revealed that strictosamide has a relatively strong binding to certain protein targets such as phosphodiesterase B1 (LmajPDEB1) (PDB: 2R8Q) and Uridine 5'-monophosphate synthase (LdUMPS) (PDB: 3QW4) among all the isolated alkaloids. Conclusion: The aerial part of Argemone mexicana yielded two benzophenanthridine alkaloids, norchelerythrine and berberine besides the tetracyclic terpenes, sitost-4-en-3-one (β-sitostenone. The extract of the root bark of Nauclea latifolia yielded the two β-carboline alkaloids, naucleficine and strictosamide besides the ubiquitous β-sitosterol. Further research is required to reveal the possible mechanism of action of the isolated compounds.
URI: http://khartoumspace.uofk.edu/123456789/26681


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