title: Stemodin-derived analogues with lipid peroxidation, cyclooxygenase enzymes and human tumour cell proliferation inhibitory activities.
abstract: A series of analogues, derived from the antiviral and cytotoxic diterpene stemodin, were prepared and evaluated for their lipid peroxidation (LPO), cyclooxygenase enzyme-1 (COX-1) and -2 (COX-2), and tumour cell proliferation inhibitory activities. Oxidation of stemodin produced stemodinone, which was then converted to stemod-12-en-2-one. Reaction of the latter under Petrow conditions (bromine; silver acetate/pyridine) yielded mainly dibrominated abeo-stachanes. Solvolysis of the dibromo compounds gave products of hydrolysis, some with rearranged skeleta. In the lipid peroxidation inhibitory assay three of the compounds exhibited prominent activity. Interestingly, all the analogues showed higher COX-1 enzyme inhibition than COX-2. Although a few of the diterpenes limited the growth of some human tumour cell lines, most compounds induced proliferation of such cells.
authors.affiliation: Department of Chemistry, The University of the West Indies, Mona, Kingston 7, Jamaica.
authors.forename: Floyd A
authors.initials: FA
authors.lastname: Russell
authors.forename: Vanisree
authors.initials: V
authors.lastname: Mulabagal
authors.forename: Dwayne R
authors.initials: DR
authors.lastname: Thompson
authors.forename: Marvadeen A
authors.initials: MA
authors.lastname: Singh-Wilmot
authors.forename: William F
authors.initials: WF
authors.lastname: Reynolds
authors.forename: Muraleedharan G
authors.initials: MG
authors.lastname: Nair
authors.forename: Vratislav
authors.initials: V
authors.lastname: Langer
authors.forename: Paul B
authors.initials: PB
authors.lastname: Reese
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D010084:Oxidation-Reduction; D028083:Scrophulariaceae / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016861:Cyclooxygenase Inhibitors; D004224:Diterpenes; C074341:stemodin