Jian-Ping Yang

Synthesis and structure–activity relationship analysis of caffeic acid amides as selective matrix metalloproteinase inhibitors

Four series of acid amides were synthesized, and through measurement using a fluorogenic substrate assay with human recombinant MMP-1, MMP-2 and MMP-9, compound 3f showed considerable inhibitory activities against MMP-2, MMP-9 and the best selectivity over MMP-1. Preliminary structure-activity relationship analysis indicated that caffeic acid amides with electron-donating groups at para-position of amino phenyl group showed better inhibitory activities and selectivity than those with electron-withdrawing groups, and the presence of adjacent dihydroxy in the caffeoyl group was very important for the MMP-2 and MMP-9 inhibitory activities.

An efficient partial synthesis of 4′-O-methylquercetin via regioselective protection and alkylation of quercetin

Summary An efficient partial 5-step synthesis of 4′-O-methylquercetin from quercetin in 63% yield is reported. This strategy relies on the selective protection of the catechol group with dichlorodiphenylmethane in diphenyl ether as solvent and on the selective protection of the hydroxyl groups at positions 3 and 7 with chloromethyl ether.

Synthesis and biological evaluation of methylated scutellarein analogs based on metabolic mechanism of scutellarin in vivo.

Scutellarin (1) could be hydrolyzed into scutellarein (2) in vivo and then converted into methylated, sulfated and glucuronidated forms. In order to investigate the biological activities of these methylated metabolites, eight methylated analogs of scutellarein (2) were synthesized via semi-synthetic methods. The antithrombotic activities of these compounds were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity. Furthermore, the physicochemical properties of these compounds including aqueous solubility and lipophilicity were also investigated. The results showed that 6-O-methylscutellarein (5) demonstrated potent antithrombotic activity, stronger antioxidant activity and balanced solubility and permeability compared with scutellarin (1), which warrants further development of 5 as a promising lead for the treatment of ischemic cerebrovascular disease.

Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism In Vivo

Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1‐diphenyl‐2‐picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2O2‐induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment.

Design, Synthesis and Biological Evaluation of Caffeic Acid Amides as Selective MMP‐2 and MMP‐9 Inhibitors

Strategy, Management and Health Policy Preclinical Research

Synthesis of scutellarein derivatives to increase biological activity and water solubility.

In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease.

Design and synthesis of novel NO-donor-ferulic acid hybrids as potential antiatherosclerotic drug candidatesa

Novel NO‐donor‐ferulic acid hybrids were designed and synthesized through a symbiotic approach using ferulic acid and three different NO‐donating groups, such as nitric ester, 4‐hydroxyl‐3‐phenylfuroxan, and 4‐hydroxymethyl‐3‐phenylsulfonylfuroxan. Antioxidant, nitric oxide release, and vasodilator properties studies showed that the target phenylsulfonylfuroxan 14, especially 14c, while keeping the antioxidant activity, showed more NO release activity and vasodilating activity than isosorbide dinitrate (ISDN). Thus, 14c may be considered a novel potent anti‐atherosclerosis drug candidate. Drug Dev Res 72: 405–415, 2011.

A New and Efficient Synthesis of 6-O-Methylscutellarein, the Major Metabolite of the Natural Medicine Scutellarin

In this paper, a new and efficient synthesis of 6-O-methylscutellarein (3), the major metabolite of the natural medicine scutellarin, is reported. Two hydroxyl groups at C-4′ and C-7 in 2 were selectively protected by chloromethyl methyl ether after the reaction conditions were optimized, then 6-O-methyl-scutellarein (3) was produced in high yield after methylation of the hydroxyl group at C-6 and subsequent deprotection of the two methyl ether groups.

Targeting the development of resveratrol as a chemopreventive agent

Tumor development consists of several separate, but closely linked, stages: tumor initiation, promotion, and progression. This long and complex process provides opportunities for intervention both in preventing cancer initiation and in treating the neoplasm during its premalignant stages. Resveratrol, a polyphenolic compound found in many plant species, including grapes, peanuts, and various herbs, has recently been investigated intensely for its cancer chemopreventive property. The present work is an overview of the chemopreventive mechanisms of resveratrol in anti‐initiation, anti‐promotion, and anti‐progression. These, together with the low toxicity of resveratrol, suggest promise for novel chemopreventive agents. However, the low bioavailability and rapid clearance of resveratrol from the circulation require the design of new resveratrol‐like chemopreventive agents, the structural modifications and the structure–activity relationship of which are also discussed in this review. Drug Dev Res 71:335–350, 2010.

An improved synthesis of 6- O -methyl-scutellarein through selective benzylation

An improved synthesis of 6-O-methyl-scutellarein is described. Benzyl bromide was selected to protect both the hydroxyl groups at C-4′ and C-7 in scutellarein. The product was then methylated and deprotected to produce the target compound in high yield in four steps.