Peganine hydrochloride dihydrate an orally active antileishmanial agent

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 9; pp. 2585 - 2586
• Main Authors: Khaliq, Tanvir, Misra, Pragya, Gupta, Swati, Reddy, K. Papi, Kant, Ruchir, Maulik, P.R., Dube, Anuradha, Narender, T.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.05.2009; Elsevier
• Subjects: Administration, Oral; Alkaloids - chemistry; Alkaloids - pharmacology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - pharmacology; Apoptosis; Biological and medical sciences; Biological Assay; Chemistry, Pharmaceutical - methods; Cricetinae; Crystallography, X-Ray - methods; Drug Design; Humans; In-vivo and in-vitro antileishmanial activity; Leishmania donovani; Leishmania donovani - metabolism; Macrophages - metabolism; Macrophages - parasitology; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Peganinehydrochloridedihydrate; Peganum - metabolism; Peganum harmala; Pharmacology. Drug treatments; Plant Extracts - metabolism; Quinazolines - chemistry; Quinazolines - pharmacology; Topoisomerase inhibition; Topoisomerase inhibition; Peganinehydrochloridedihydrate; In-vivo and in-vitro antileishmanial activity; Apoptosis; Seeds; Leishmania donovani; Antiprotozoal agent; Alkaloid; Isomerases; Hydrochlorides; Zygophyllaceae; Dicotyledones; Angiospermae; Inhibition; Hydrates; Kinetoplastida; Protozoa; Enzyme; Rodentia; DNA topoisomerase; Oral administration; In vitro; Biological activity; In vivo; Vertebrata; Mammalia; Mouse; Animal; Plant origin; In-vivo and In-vitro antileishmanial activity; Parasiticide; Isolation; Spermatophyta
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.03.039

Protozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on Peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2D-NMR spectral data and single crystal X-ray crystallography data indicated 1 as peganine hydrochloride in dihydrated form. The compound 1 exhibited in-vitro activity against both extracellular promastigotes as well as intracellular amastigotes residing within murine macrophages in Leishmania donovani. Furthermore, 1 also exhibited in-vivo activity, 79.6 (±8.07)% against established VL in hamsters at a dose of 100 mg/kg b.wt.