title: Polyoxygenated Cyclohexenes and Other Constituents of Cleistochlamys kirkii Leaves.
abstract: Thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol B (3), cleistenechlorohydrins A (4) and B (5), cleistenediols A-F (6-11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15-21) were isolated from a MeOH extract of the leaves of Cleistochlamys kirkii. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of compounds 1, 17, and 19 were established by single-crystal X-ray diffraction. The configuration of the exocyclic double bond of compound 2 was revised based on comparison of its NMR spectroscopic features and optical rotation to those of 1, for which the configuration was determined by X-ray diffraction. Observation of the co-occurrence of cyclohexenoids and heptenolides in C. kirkii is of biogenetic and chemotaxonomic significance. Some of the isolated compounds showed activity against Plasmodium falciparum (3D7, Dd2), with IC50values of 0.2-40 μM, and against HEK293 mammalian cells (IC502.7-3.6 μM). While the crude extract was inactive at 100 μg/mL against the MDA-MB-231 triple-negative breast cancer cell line, some of its isolated constituents demonstrated cytotoxic activity with IC50values ranging from 0.03-8.2 μM. Compound 1 showed the most potent antiplasmodial (IC500.2 μM) and cytotoxic (IC500.03 μM, MDA-MB-231 cell line) activities. None of the compounds investigated exhibited translational inhibitory activity in vitro at 20 μM.
authors.affiliation: Department of Chemistry, College of Natural and Applied Sciences, University of Dar es Salaam , P.O. Box 35061, Dar es Salaam, Tanzania.|Department of Chemistry and Molecular Biology, University of Gothenburg , SE-412 96 Gothenburg, Sweden.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Nyandoro
authors.affiliation: Department of Chemistry, College of Natural and Applied Sciences, University of Dar es Salaam , P.O. Box 35061, Dar es Salaam, Tanzania.
authors.forename: Joan J E
authors.initials: JJ
authors.lastname: Munissi
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , SE-412 96 Gothenburg, Sweden.|Sahlgrenska Cancer Centre, University of Gothenburg , Gothenburg, SE-405 30, Sweden.
authors.forename: Amra
authors.initials: A
authors.lastname: Gruhonjic
authors.affiliation: Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University , Nathan, Q1d 4111, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Duffy
authors.affiliation: University of Jyvaskyla, Department of Chemistry, Nanoscience Center, University of Jyvaskyla , P.O. Box. 35, Jyvaskyla FI-40014, Finland.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Pan
authors.affiliation: University of Jyvaskyla, Department of Chemistry, Nanoscience Center, University of Jyvaskyla , P.O. Box. 35, Jyvaskyla FI-40014, Finland.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Puttreddy
authors.affiliation: Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University , Nathan, Q1d 4111, Australia.
authors.forename: John P
authors.initials: JP
authors.lastname: Holleran
authors.affiliation: Sahlgrenska Cancer Centre, University of Gothenburg , Gothenburg, SE-405 30, Sweden.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fitzpatrick
authors.affiliation: Department of Biochemistry, McGill University , Montreal, QC, H3G 1Y6, Canada.
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University , Nathan, Q1d 4111, Australia.
authors.forename: Vicky M
authors.initials: VM
authors.lastname: Avery
authors.affiliation: University of Jyvaskyla, Department of Chemistry, Nanoscience Center, University of Jyvaskyla , P.O. Box. 35, Jyvaskyla FI-40014, Finland.
authors.forename: Kari
authors.identifier: 0000-0002-7282-8419
authors.initials: K
authors.lastname: Rissanen
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg , SE-412 96 Gothenburg, Sweden.|Swedish NMR Centre, University of Gothenburg , Gothenburg, SE-405 30, Sweden.
authors.forename: Máté
authors.identifier: 0000-0003-0359-5970
authors.initials: M
authors.lastname: Erdélyi
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy*; D053138:Cyclohexenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D057809:HEK293 Cells / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D014961:X-Ray Diffraction
chemical_list: D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D053138:Cyclohexenes; C000621500:cleistenechlorohydrin A; C000621501:cleistenechlorohydrin B