Renren Bai

Total synthesis and antihypertensive activity of (±)7,8-dihydroxy-3-methyl-isochromanone-4

This letter describes the total synthesis, preliminary biological evaluation and mechanism studies of a novel and structurally unique isochromanone, (+/-)7,8-dihydroxy-3-methyl-isochromanone-4 (1), a nature product contained in banana (Musa sapientum L.) peel. The bioassay showed that compound 1 displays potent antihypertensive activity in renal hypertensive rats and further mechanism studies revealed that it is an ACE inhibitor.

Novel nitric oxide-releasing isochroman-4-one derivatives: Synthesis and evaluation of antihypertensive activity.

By coupling nitric oxide (NO)-donor moieties with a natural antihypertensive product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] and its analogue (±)-XJP-B, a series of novel NO-releasing isochroman-4-one derivatives were designed and synthesized. The NO-releasing assay indicated that compounds Ia, Id, IIIb and IIIe released the maximum amount of NO. The maximum reductions of blood pressure of Ia, IIIb and IIIe in SHRs were nearly 40%, which was obviously superior to that of the lead compounds and comparable to that of reference drug captopril. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel antihypertensive agents.

Design, synthesis and antioxidant activity evaluation of novel β-elemene derivatives

Forty β-elemene derivatives were prepared and their antioxidant activity in H2O2-treated human umbilical vein endothelial cells (HUVECs) was first investigated. Among which, the dimer compounds 5r and 5s exhibited the most potent antioxidant activity against reactive oxygen species production. Meanwhile, 5r and 5s led to a significant increase in superoxide dismutase and nitric oxide levels and decrease in malonyldialdehyde and lactate dehydrogenase contents. Furthermore, MTT assay showed that 5r and 5s did not produce obvious cytotoxicity and had significantly cytoprotective effects against oxidative damage on HUVECs.

Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates

A series of novel 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives were designed and synthesized to develop new angiotensin II subtype 2 (AT2) receptor agonists as novel antihypertensive candidates. It was found that 14f (IC50=0.4 nM) and 15e (IC50=5.0 nM) displayed potent AT2 receptor affinity and selectivity in binding assays. Biological evaluation in vivo suggested that 14f is obviously superior to that of reference drug losartan in RHRs, and meanwhile, 14f has no significant impact on heart rate. The interesting activities of these compounds may make them promising candidates as antihypertensive agents.

Chiral separation, configurational identification and antihypertensive evaluation of (±)-7,8-dihydroxy-3-methyl-isochromanone-4

(±)-7,8-Dihydroxy-3-methyl-isochromanone-4 [(±)-XJP] is a natural antihypertensive product contained in banana (Musa sapientum L.) peel. (-)-XJP and (+)-XJP were first obtained by chiral resolution, meanwhile circular dichroism (CD) calculations and chiral synthesis were employed to investigate the absolute configuration. The results indicated that the absolute configuration of (+)-XJP is S-configured and the absolute configuration of (-)-XJP is R-configured. Furthermore, the evaluation of antihypertensive effects in vivo proved that R-(-)-XJP was more potent than S-(+)-XJP and [(±)-XJP].

Synthesis and β-adrenergic blocking activity of oxime ether hybrids derived from a natural isochroman-4-one

AIM In a search for new cardiovascular drug candidates, a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized. METHOD Compounds 3 and 6, derived from the natural antihypertensive compound 7, 8-dihydroxy-3-methyl-isochroman-4-one (XJP), were designed and synthesized. Subsequently, a series of novel isochroman-4-one oxime ether hybrids were prepared by hybridizing various N-substituted isopropanolamine functionalities to isochroman-4-one oxime. Furthermore, β1-adrenergic blocking activities of the synthesized compounds were assayed using the isolated rat left atria. RESULTS Twenty target compounds were obtained, and the preliminary structure-activity relationships were deduced. The most promising compound Ic exhibited β1-adrenoceptor blocking activity (inhibition: 52.2%) at 10(-7) mol·L(-1), which was superior to that of propranolol (inhibition: 49.7%). CONCLUSION The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.

Synthesis of 13-β-elemene ester derivatives and evaluation of their antioxidant activity in human umbilical vein endothelial cells.

In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.