title: Vascular L-type Ca²⁺ channel blocking activity of sulfur-containing indole alkaloids from Glycosmis petelotii.
abstract: In the search for novel natural compounds endowed with potential antihypertensive activity, a new sulfur-containing indole alkaloid, N-demethylglypetelotine (2), and its known analogue glypetelotine (1), were isolated from the leaves of Glycosmis petelotii. Their structures were established on the basis of spectroscopic evidence. The two alkaloids were assessed for vasorelaxing activity on rat aorta rings and for L-type Ba(2+) current [I(Ba(L))] blocking activity on single myocytes isolated from rat tail artery. Both glypetelotine and N-demethylglypetelotine inhibited phenylephrine-induced contraction with IC50 values of 20 and 50 μM, respectively. The presence of endothelium did not modify their spasmolytic effect. Neither glypetelotine nor N-demethylglypetelotine affected Ca(2+) release from the sarcoplasmic reticulum induced by phenylephrine. The spasmolytic effect of glypetelotine increased with membrane depolarization. In the presence of 60 mM K(+), both compounds inhibited, in a concentration-dependent manner, the contraction induced by cumulative addition of Ca(2+), this inhibition being inversely related to Ca(2+) concentration. Glypetelotine and, less efficiently N-demethylglypetelotine, inhibited I(Ba(L)), the former compound also affecting I(Ba(L)) kinetics. In conclusion, glypetelotine is a novel vasorelaxing agent which antagonizes L-type Ca(2+) channels.
authors.affiliation: Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology , 18 Hoang Quoc Viet Street, 122100 Cau Giay, Hanoi Vietnam.
authors.forename: Nguyen Manh
authors.initials: NM
authors.lastname: Cuong
authors.forename: Pham Ngoc
authors.initials: PN
authors.lastname: Khanh
authors.forename: Pham Thu
authors.initials: PT
authors.lastname: Huyen
authors.forename: Ho Viet
authors.initials: HV
authors.lastname: Duc
authors.forename: Tran Thu
authors.initials: TT
authors.lastname: Huong
authors.forename: Vu Thi
authors.initials: VT
authors.lastname: Ha
authors.forename: Miriam
authors.initials: M
authors.lastname: Durante
authors.forename: Giampietro
authors.initials: G
authors.lastname: Sgaragli
authors.forename: Fabio
authors.initials: F
authors.lastname: Fusi
mesh_terms: D000465:Algorithms; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010276:Parasympatholytics / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D027821:Rutaceae / Q000737:chemistry*; D013457:Sulfur Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014744:Vietnam
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D026121:Indole Alkaloids; C000591555:N-demethylglypetelotine; D010276:Parasympatholytics; D013457:Sulfur Compounds; D014665:Vasodilator Agents; C000591556:glypetelotine; D010656:Phenylephrine