ABSTRACT
In order to establish structure-activity relationships, nine neo-clerodane diterpenes isolated from the acetone extract of aerial parts of Baccharis flabellata Hook & Arn var. fabellata were assayed for antifeedant activity against Tribolium castaneum (Coleoptera: Tenebrionidae). Compounds exhibiting maximal antifeedant activities showed an alpha,beta-unsaturated carbonyl group on the decalin portion and a furan ring at the side chain. Stereoelectronic studies indicate that the distance between the furan heteroatom and the more electrophilic carbon of the decaline moiety, as well as the electrostatic charge on that atom, were important features for antifeedant activity. Compounds possesing an alpha,beta,gamma,delta-unsaturated carbonyl group or an acetoxyl group at C-2, were inactive. Theoretical calculations were performed in order to find some structure-activity relationships.
Subject(s)
Baccharis/chemistry , Diterpenes, Clerodane/chemistry , Diterpenes, Clerodane/pharmacology , Tribolium/drug effects , Animals , Diterpenes, Clerodane/isolation & purification , Feeding Behavior/drug effects , Molecular Conformation , Nuclear Magnetic Resonance, Biomolecular , Optical Rotation , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Structure-Activity Relationship , Tribolium/physiologyABSTRACT
The preventive effect of natural xanthanolides as well as a series of synthetic derivatives on ulcer formation induced by absolute ethanol in rats was examined. Among the compounds tested, xanthatin gave the strongest protective activity. The inhibitory action exerted by this molecule on the lesions induced by 0.6N HCl and 0.2N NaOH was highly significant, reducing ulceration in the range of 58-96% at a dose from 12.5 to 100mg/kg. These results appear to confirm that the presence of a non-hindered alpha,beta-unsaturated carbonyl group seems to be an essential structural requirement for the gastric cytoprotective activity of these compounds. In order to explore this possibility, a theoretical conformational analysis was performed. We suggest that the mechanism of protection would involve, at least in part, a nucleophylic attack of the sulfhydryl group from the biological molecules present in the gastric mucosa to electrophylic carbons accessible in suitable Michael acceptors.
Subject(s)
Anti-Ulcer Agents/pharmacology , Sesquiterpenes/pharmacology , Xanthium/chemistry , Animals , Anti-Ulcer Agents/chemistry , Central Nervous System Depressants , Chemical Phenomena , Chemistry, Physical , Ethanol , Hydrochloric Acid , Magnetic Resonance Spectroscopy , Male , Models, Molecular , Molecular Conformation , Monte Carlo Method , Plant Extracts/chemistry , Rats , Rats, Wistar , Sesquiterpenes/chemistry , Sodium Hydroxide , Stomach Ulcer/chemically induced , Stomach Ulcer/prevention & control , Structure-Activity RelationshipABSTRACT
Growth inhibitory activities and nutritional indices of catalpol (1), 8-O-acetylharpagide (2), and harpagide (3) were determinated in larvae and adults of Tribolium castaneum, respectively. Compound 1 produced a series of allelochemical effects probably related with the DNA synthesis. This iridoid possessed the highest inhibitory activity against DNA polymerase. Molecular orbital calculations suggest that a pi-pi charge transfer recognition model could explain the action of iridioids toward nucleic acid synthesis.
Subject(s)
Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Glucosides/isolation & purification , Glucosides/pharmacology , Insect Control , Iridoids/isolation & purification , Iridoids/pharmacology , Nucleic Acid Synthesis Inhibitors , Nucleic Acid Synthesis Inhibitors/isolation & purification , Nucleic Acid Synthesis Inhibitors/pharmacology , Pyrans/isolation & purification , Pyrans/pharmacology , Tribolium/drug effects , Animals , Enzyme Inhibitors/chemistry , Glucosides/chemistry , Iridoid Glucosides , Iridoid Glycosides , Iridoids/chemistry , Larva/drug effects , Models, Molecular , Molecular Structure , Nucleic Acid Synthesis Inhibitors/chemistry , Pyrans/chemistryABSTRACT
Two clerodane-type diterpene glycosides esters, which were studied as peracetyl derivatives, together with the known diterpene marrubiagenine, were isolated from the aerial part of Baccharis sagittalis (Less). Their structures were established by spectroscopic methods. Antifeedant activity toward Tenebrio molitor larvae of the isolated compounds along with six other diterpenes was evaluated and some structure-antifeedant bioactivity relationships are reported.
