title: Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases.
abstract: This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhuang
authors.affiliation: Department of Health, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, People's Republic of China.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Liao
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiao-Bian
authors.initials: XB
authors.lastname: Dong
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Du
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xin-Xue
authors.initials: XX
authors.lastname: Liao
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Wang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D002302:Cardiac Output / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D020128:Inhibitory Concentration 50; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D017706:Lisinopril; D003474:Curcumin
keywords: ACE inhibition; antihypertensive; bioavailability; curcumin; synthesis; vasodilation