title: Synthesis and vasodilator effects of rutaecarpine analogues which might be involved transient receptor potential vanilloid subfamily, member 1 (TRPV1).
abstract: Rutaecarpine is the major alkaloid component of Wu-Chu-Yu, a well known Chinese herbal drug. It has been reported that rutaecarpine causes the vasodilator, hypotensive effects by stimulation of CGRP synthesis and release via activation of TRPV1. In present study, 23 rutaecarpine analogues were designed and synthesized. Then, the vasodilator effects of theses compounds were screened by rat aortic ring experiment. The result showed that the 14-N atom of rutaecarpine might be the key site for the activity. The 5-carbonyl might make lower contribution to the effect. And simple substitute in indole-ring or quinazoline-ring would not enhance the vasodilator effect unless in proper position with proper group. One of these compounds, 10-methylrutaecarpine, exhibited similar effect with rutaecarpine. Further functional experiments showed its vasodilator and hypotensive effect were related to the stimulation of CGRP release via activation of TRPV1. The vasodilator effects of these compounds were evaluated and the structure-activity relationship was elucidated for the first time. The results suggested a new direction of valuable TRPV1 agonist as anti-hypertensive drugs.
authors.affiliation: Chemistry Section, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, No. 172, Tong Zi Po Road, Changsha 410013, Hunan, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.forename: Gaoyun
authors.initials: G
authors.lastname: Hu
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Li
authors.forename: Huayong
authors.initials: H
authors.lastname: Zhou
authors.forename: Ye
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D050916:TRPV Cation Channels / Q000502:physiology*; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052999:Quinazolinones
chemical_list: D026121:Indole Alkaloids; D011799:Quinazolines; D050916:TRPV Cation Channels; D014665:Vasodilator Agents; C493922:Trpv1 protein, rat; C028632:rutecarpine; D052999:Quinazolinones