A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii

Stephen  S. Nyandoro; Gasper Maeda; Joan  J.E. Munissi; Amra Gruhonjic; Paul  A. Fitzpatrick; Sofia Lindblad; Sandra Duffy; Jerry Pelletier; Fangfang Pan; Rakesh Puttreddy; Vicky  M. Avery; Máté Erdélyi

doi:10.3390/molecules24152746

Molecules (Jul 2019)

A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii

Stephen S. Nyandoro,
Gasper Maeda,
Joan J.E. Munissi,
Amra Gruhonjic,
Paul A. Fitzpatrick,
Sofia Lindblad,
Sandra Duffy,
Jerry Pelletier,
Fangfang Pan,
Rakesh Puttreddy,
Vicky M. Avery,
Máté Erdélyi

Affiliations

Stephen S. Nyandoro: Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, Dar es Salaam P.O. Box 35061, Tanzania
Gasper Maeda: Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, Dar es Salaam P.O. Box 35061, Tanzania
Joan J.E. Munissi: Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, Dar es Salaam P.O. Box 35061, Tanzania
Amra Gruhonjic: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden
Paul A. Fitzpatrick: Sahlgrenska Cancer Centre, University of Gothenburg, SE-405 30 Gothenburg, Sweden
Sofia Lindblad: Department of Chemistry-BMC, Uppsala University, SE-751 23 Uppsala, Sweden
Sandra Duffy: Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan Q1d 4111, Australia
Jerry Pelletier: Department of Biochemistry, McGill University, Montréal, QC H3G 1Y6, Canada
Fangfang Pan: Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, College of Chemistry, Central China Normal University, Luoyu Road 152, Wuhan 430079, China
Rakesh Puttreddy: Department of Chemistry, University of Jyvaskyla, P.O. Box 35, FI-40014 Jyvaskyla, Finland
Vicky M. Avery: Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan Q1d 4111, Australia
Máté Erdélyi: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden

DOI: https://doi.org/10.3390/molecules24152746
Journal volume & issue: Vol. 24, no. 15
p. 2746

Abstract

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Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2−13). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds 5 and 10 were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of C. kirkii root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite Plasmodium falciparum at 0.01 μg/mL. The isolated metabolites dichamanetin, (E)-acetylmelodorinol, and cleistenolide showed IC50 = 9.3, 7.6 and 15.2 μM, respectively, against P. falciparum 3D7. Both the crude extract and the isolated compounds exhibited cytotoxicity against the triple-negative, aggressive breast cancer cell line, MDA-MB-231, with IC50 = 42.0 μg/mL (crude extract) and 9.6−30.7 μM (isolated compounds). Our findings demonstrate the potential applicability of C. kirkii as a source of antimalarial and anticancer agents.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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