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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 ?M. 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.

SUBMITTER: Zhuang XD

PROVIDER: S-EPMC4708961 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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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.

Zhuang Xiao-Dong XD Liao Li-Zhen LZ Dong Xiao-Bian XB Hu Xun X Guo Yue Y Du Zhi-Min ZM Liao Xin-Xue XX Wang Li-Chun LC

Drug design, development and therapy 20160105

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 120.3 ...[more]

PMID: 26792980

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Project description:INTRODUCTION:Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. PURPOSE:This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. METHODS:The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. RESULTS:The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and ?-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. CONCLUSION:The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and ?-blockers and/or having complementary modes of action.

Dataset Information

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.

Publications

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.

Similar Datasets

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