ABSTRACT
Virginiamycin acetyltransferase D (VatD) plays a vital rule in streptogramins resistance by chemically inactivating streptogramin A. Therefore, it is desirable to discover novel small molecular weight inhibitors of VatD via state-of-the-art virtual screening techniques. This "cocktail" strategy by combining VatD inhibitor with streptogramins may provide new therapeutic opportunity for resistant bacteria infections. Structure-based virtual screening method (molecular docking) was applied to rank and score a chemical database containing 300 000 commercially available compounds against the VatD substrate binding site. Twenty six out of the 200 top scored compounds from the docking calculation were selected and submitted to the VatD enzymatic inhibition assay. The plasmid pRSET B/vatD was constructed and transformed into E.coli (trxB) host cells for over-expression, and VatD enzyme was purified and validated by showing acetyltransferase activity to Virginiamycin M1. Three out of these 26 tested compounds showed enzymatic inhibition on VatD with IC50 168.6, 91.0 and 55.2 μmol·L-1, separately. Other compounds could not be dissolved in the system and/or had little effect on the enzyme (IC50>200 μmol·L-1). To our knowledge, it is first time that small molecular weight organic compounds were identified as VatD inhibitors. It is expected that the VatD inhibitors identified at present study could serve as lead compounds for the further development of the novel therapeutic agents to overcome streptogramins resistance.
ABSTRACT
Results of experiments such as ammonia steaming test in mice and citr ic acid test in guinea pigs, phenol red secretion test in mice and capillary exp ectorant test in rats, in-vivo and in-vitro antiasthmatic tests in guinea pigs p roved that Tankeqing capsule had good antitussive, expectorant and antiasthmatic effects and a significant time-effect relationship was showed. The antitussive effect and expectorant effect arrived to the peak in 1-6h after oral administrat ion, and the antiashmatic effect in about 1h.
ABSTRACT
Objective To study the bioactive components from stems of Schisandra propinqua var. intermedia. Methods Compounds were separated with acombination of multi-chromatography. Their che- mical structures were determined on the basis of spectral analysis and chemical evidence. Results Nine compounds were isolated from S. propinqua var. intermedia. The structures were elucidated as vanillic acid- 4- O-?-D-allopyranoside (Ⅰ), salidroside (Ⅱ), 2-hydroxy-5-(2-hydroxyethyl)-phenyl-?-D-glucopyranoside (Ⅲ), 3, 4-dimethoxyphenyl-4-?-D-glucopyranoside (Ⅳ), 3, 5-dihydroxybenzoic acid-4-O-?-D-glucopyranoside (Ⅴ), 3, 5-dimethoxy-4-hydroxy-benzoic acid (Ⅵ), 4-methoxy-benzoic acid (Ⅶ), vanillic acid (Ⅷ) and protocatechuic acid (Ⅸ). Conclusion Compound Ⅰ is a new phenolic alloside and others are isolated from S. propinqua var. intermedia for the first time.
ABSTRACT
Results of experiments such as ammonia steaming test in mice and citric acid test in guinea pigs, phenol red secretion test in mice and capillary expectorant test in rats, in-vivo and in-vitro antiasthmatic tests in guinea pigs proved that Tankeqing capsule had good antitussive, expectorant and antiasthmatic effects and a significant time-effect relationship was showed. The antitussive effect and expectorant effect arrived to the peak in 1-6h after oral administration, and the antiashmatic effect in about 1h.