Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as-adrenoceptor antagonists

Chiral drug naftopidil (NAF), a specific-adrenoceptor (AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the-AR, but the binding mechanism of these two stereochemical NAF isomers to thereceptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data ofandenantiomers matched satisfactorily the pharmacophore model for-selective antagonists. Based on the constructedhomology model, molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.

Study on the Relieving Cough and Eliminating Phlegm Effects of Stemoninine Combined with Mogroside Ⅴ on Mice / 中国药房

OBJECTIVE:To study the relieving cough and eliminating phlegm effects of stemoninine combined with mogrosideⅤ on mice,and select its optimal ratio. METHODS:70 mice were selected in each experiment and randomly divided into 7 groups,namely solvent group(normal saline), codeine(15 mg/kg)or ambroxol(30 mg/kg)group(positive control),stemoni-nine group(30 mg/kg),mogroside Ⅴ group(30 mg/kg),stemoninine-mogroside Ⅴ combination group(30 mg/kg)with mass ra-tio of 2:1,1:1,1:2,ig,once a day. Ammonia-induced cough experiment(positive drug was codeine)and tracheal phenol red ex-cretion experiment(positive drug was ambroxol)were respectively conducted. Using cough latent period,cough times and volume of tracheal phenol red excretion as indexes,the antitussive and expectorant effects of drug in each group were compared. RE-SULTS:Compared with solvent group,cough latent period was obviously shortened,cough times was obviously reduced,volume of tracheal phenol red excretion was obviously increased in each administration group(P<0.05 or P<0.01). Compared with mogro-side Ⅴ group,cough latent period was obviously shortened,cough times was obviously reduced in stemoninine-mogroside Ⅴgroup with different mass ratios(P<0.05),and 2:1,1:1 groups showed the best effects. Compared with stemoninine group,vol-ume of tracheal phenol red excretion was obviously increased in stemoninine-mogroside Ⅴ group with different mass ratios (P<0.05),and 1:1,1:2 groups showed the best effects. CONCLUSIONS:The combination of temoninine and mogroside Ⅴ shows synergistic effects on relieving cough and eliminating phlegm,stemoninine-mogrosideⅤmass ratio of 2:1,1:1 can be used as pre-ferred combination of reference.

Chemical constituents from Callicarpa kwangtungensis Chun / 中国药科大学学报

@#Nine compounds were isolated from the aerial part of Callicarpa kwangtungensis chun by various column chromatographic methods. Their structures were identified as pinnatifidanoid A(1), blumenol C(2), megastigman-5- ene-3β, 9R-diol(3), 3β-hydroxyurs-12-en-28-oic acid(4), kaji-ichigoside F1(5), 1, 4-terephthalic acid(6), syringic acid(7), vanillic acid(8), and 3, 5-dimethoxy-4-methylbenzyl alcohol(9)on the basis of spectral analysis. C13 nor-isoprenoids of 1-3, and compounds 5, 6 and 9, were isolated from the genus Callicarpa for the first time.

Chemical constituents of Taxus chinensis var. mairei cell cultures / 药学学报

The chemical constituents of Taxus chinensis var. mairei cell cultures were investigated by chromatographic methods, including silica gel column chromatography, Sephadex LH-20 and preparative HPLC. Thirteen compounds were isolated from the 80% ethanol extract of cultured cells and their structures were elucidated by spectral data and physicochemical properties, which were identified as 2α,4α,7β,9α,10β-pentaacetoxy-14β-hydroxytax-11-ene (1), 2α,4α,7β,9α,10β-pentaacetoxytax-11-ene (2), 1β-deoxybaccatin VI (3), 2α-acetoxytaxusin (4), taxuyunnanine C (5), yunnanxane (6), 2α,5α,10β-triacetoxy-14β-propionyloxy-4 (20), 11-taxadiene (7), 2α,5α,10β-triacetoxy-14β-isobutyryloxy-4 (20), 11-taxadiene (8), 2α,5α,10β-triacetoxy-14β-(2'-methyl)butyryloxy-4 (20), 11-taxadiene (9), 13-dehydroxylbaccatin III (10), 13-dehydroxy-10-deacetylbaccatin III (11), paclitaxel (12) and (13) β-sitosterol. Among them, compound 1 is a new compound, and compounds 2, 4, 10 and 11 are isolated from the cell culture of Taxus chinensis var. mairei for the first time.