Development of Orally Active Thrombin Inhibitors for the Treatment of Thrombotic Disorder Diseases.

Thrombotic disorders represent the major share of the various cardiovascular diseases, and significant progress has been made in the development of synthetic thrombin inhibitors as new anticoagulants. In addition to the development of highly potent and selective inhibitors with improved safety and suitable half-life, several allosteric inhibitors have been designed and synthesized, that did not fully nullify the procoagulant signal and thus could result in reduced bleeding complications. Furthermore, natural products with thrombin inhibitory activity have been isolated, and some natural products have been modified in order to improve their inhibitory activity and metabolic stability. This review summarizes the development of orally active thrombin inhibitors for the treatment of thrombotic disorder diseases, which could serve as a reference for the interested researchers.

Total synthesis and anti-viral activities of an extract of Radix isatidis.

Radix isatidis (Banlangen), a famous traditional Chinese medicine, has been used for thousands of years in China due to its anti-viral activity. Through our research, we inferred that the anti-viral activity of Radix isatidis depended on the water-soluble part. Among the components of this extract, the isoquinoline derivative 1 was isolated for the first time and has shown better anti-viral activity than other constituents. In this study, to solve the problem of sourcing sufficient quantities of compound 1, a total synthesis route is described, and several analogues are also evaluated for their anti-viral activities. Among them, compound 8 shown potent anti-viral activity with an IC50 value of 15.3 µg/mL. The results suggested that isoquinoline derivatives possessed potent anti-viral activity and are worthy further development.

New sphingolipids from the root of Isatis indigotica and their cytotoxic activity.

Two new sphingolipids were isolated from the 95% EtOH extract of traditional Chinese medicinal plant Isatis indigotica. Their structures were elucidated as (2S,3R)-3-hydroxymethyl-N-(2'-hydroxynonacosanoyl)-trideca-9E-sphingenine(1) and 1-O-beta-D-glucopyranosyl-(2S,3R)-3-hydroxymethyl-N-(2'-hydroxynonacosanoyl)-trideca-9E-sphingenine(2) on the basis of spectroscopic data. Their cytotoxic effects were evaluated by using MTT method.

[Chemical constituents from water extract of Radix isatidis].

AIM: To study the chemical constituents from water extract of Radix isatidis. (Isatis indigotica Fort. ). METHODS: The water extract was underwent absorption by D101 macroporous resin, the portion eluted by ethanol of different concentrations was isolated and purified on silica gel column repeatedly. The obtained compounds were identified and structurally elucidated by their physico-chemical properties and spectral analysis. RESULTS: Five compounds were isolated from water extract of Radix isatidis, and were partly identified separately: 3-[2'-(5'-hydroxymethyl) furyl] -1 (2H) -isoquinolinone-7-O-beta-D-glucoside (I), lariciresinol-4,4'-di-O-beta-D-glucopyranoside (II), lariciresinol-4-O-beta-D-glucopyranoside (III), 2-hydroxy-1, 4-benzenedicarboxylic acid (IV), mannitol (V). CONCLUSION: Compound I is a new compound and compounds IV and V were isolated from the plant for the first time.

[Zero-fluoroscopy catheter ablation for idiopathic premature ventricular contractions from the aortic sinus cusp].

OBJECTIVE: To compare the safety, feasibility, and efficacy of a completely nonfluoroscopic approach to radiofrequency catheter ablation (RFCA) using CARTO3 and ablation with conventional fluoroscopic guidance for treatment of idiopathic premature ventricular contractions from the aortic sinus cusp (ASC-PVCs). METHODS: From April 2013 to October 2015, we prospectively enrolled 52 consecutive patients with ASC-PVCs scheduled for either CARTO3 mapping-guided zero-fluoroscopy ablation (group A, n=23) or conventional fluoroscopic ablation (group B, n=29). The success rates, rates of complications, rates of recurrences, number of radiofrequency applications, procedure time, mapping time and fluoroscopy time were compared between the 2 groups. RESULTS: s No significant differences were found in the success rates between the 2 groups [22/23 (96%) vs 24/29 (83%), P=0.21]. No major complications occurred during the procedures in either group. There was no significant difference with regard to the procedure time between the two groups (79.6∓8.8 vs 77.4∓7.2 min, P=0.332). The procedure was completed without any fluoroscopy use in group A, while the mean fluoroscopy time in group B was 23.1∓6.0 min. Group A showed a shorter mapping time than group B (4.3∓1.7 vs 7.8∓2.6 min, P<0.01) with significantly fewer radiofrequency applications (4.8∓1.1 vs 7.9∓3.2, P<0.01). The recurrence rates were comparable between the two groups over a follow-up period of 5 to 20 months. CONCLUSION: Compared with the conventional fluoroscopic technique, the zero-fluoroscopy approach can shorten the total procedure time and the ablation time with significantly reduced RF applications to eliminate ionizing radiation exposure in RFCA. RFCA guided by CARTO3 system without fluoroscopy is feasible, safe, and effective for treatment of ASC-PVCs.