title: The antagonistic effects of khellactones on platelet-activating factor, histamine, and leukotriene D4.
abstract: Khellactones of Peucedanum praeruptorum DUUN., including praeruptorins A (= Pd-Ia, 2) and B (= Pd-II,11), had an antagonistic effect specifically on platelet aggregation induced by platelet activating factor (PAF) among various aggregating agents examined, and represent a new class of PAF antagonists. We examined the effects of twenty compounds on PAF-induced platelet aggregation and on histamine- and leukotriene D4 (LTD4)-induced contractions in isolated guinea pig ileum. Compounds 2, (+/-)-cis-3',4'-diacetylkhellactone (3), (+/-)-cis-4'-acetyl-3'-crotonoylkhellactone (5), (+/-)-cis-4'-acetyl-3'-tetrolylkhellactone (6), (+/-)-cis-4'-acetyl-3'-tigloylkhellactone (7), (+/-)-cis-4'-acetyl-3'-(2"-methylbutyryl)khellactone (8), (+/-)-cis-3',4'-ditigloylkhellactone (10), and 11 all strongly inhibited PAF-induced platelet aggregation. (+/-)-cis-4'-Acetyl-3'-(2"-methyl-2"-dodecenoyl)khellactone (9), (+/-)-cis-4'-ethyl-3'-tigloylkhellactone (13), (+/-)-cis-4'-ethyl-3'-[N-(2"-triethylammonio)ethylcarbamoyl] khellactone iodide (16), (+/-)-trans-3',4'-diacetylkhellactone (18), (+/-)-trans-4'-acetyl-3'-crotonoylkhellactone (19), (+/-)-trans-4'-acetyl-3'-valerylkhellactone (20), (+/-)-trans-4'-acetyl-3'-isovalerylkhellactone (21), and (+/-)-trans-4'-acetyl-3'-tigloylkhellactone (22) were weakly inhibitory. Most of the compounds exhibited noncompetitive antagonist actions on histamine- and LTD4-induced contractions.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Showa College of Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Aida
authors.forename: T
authors.initials: T
authors.lastname: Kasama
authors.forename: N
authors.initials: N
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Tobinaga
mesh_terms: D000818:Animals; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004347:Drug Interactions; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D006633:Histamine Antagonists; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D017998:Leukotriene D4; D006632:Histamine