Anti-MRSA activities of cycloberberine derivatives with a novel chemical scaffold / 药学学报

Using CBBR as the parent core constructed in our lab, we designed and synthesized 15 novel compounds with diverse structures for evaluation of anti-bacterial activities. Structure activity relationship studies revealed that ① ring C was essential for the activity; ② 7,8- or 8,13-disubstituted CBBR derivatives showed ideal activities, weaker or similar to those corresponding to 7-, 8-, or 13-monosubstituted CBBR derivatives. Among those, compound 9a showed the most potential activity against MRSA/VISA isolates with MIC values of 1-2 μg·mL-1, much better than Lev. 9a also displayed higher stability in the plasma and liver microsomes. Molecular docking indicated that 9a might target bacterial DNA Topo IV ParE subunit, indicating a mode of action distinct from current antibacterial drugs on market. The results provided key scientific evidence for developing such compounds into a new family of anti-MRSA drugs.

Study on the Potential Targets of Guizhi Decoction Regulating Ying and Wei Based on Reverse Molecular Docking Technology / 中国药房

OBJECTIVE:To study the potential targets of Guizhi decoction regulating Ying and Wei based oncorrespondence between formulation and syndromerelationship and reverse molecular docking technology. METHODS:Active ingredients related to Guizhi decoction were obtained by literature retrievals,and PharmMapper Server was used for reverse molecular docking for ac-tive ingredients. The potential receptors of Guizhi decoction were found on the basis of docking scores,then AutoDock Vina was conducted for positive molecular docking test to observe the affinity between the ligand and the receptor molecule. 75 rats were ran-domly divided into normal group,model group,Guizhi decoction high-dose,medium-dose,low-dose groups(12,8,4 g/kg),15 in each group. Except for normal group,rats in other groups were induced for models with disharmony between Ying and Wei. Af-ter modeling,rats were intragastrically administrated once a day,for 5 d. After administration,11β-HSD1 expression levels in adi-pose tissue and muscle tissue of rats were detected. RESULTS:Reverse molecular docking for active ingredients of Guizhi decoc-tion found that 11β-HSD1 was the frequent receptor,and positive docking test confirmed that uralsaponin b,glycyrrhetnic acid and carbenoxolone and so on had higher affinity with 11β-HSD1. Results of animal test showed,compared with normal group,11β-HSD1 expression levels in adipose tissue and muscle tissue in model group were increased (P<0.05);and compared with model group,11β-HSD1 expression levels in adipose tissue and muscle tissue in Guizhi decoction high-dose group were decreased (P<0.05). CONCLUSIONS:Guizhi decoction regulating Ying and Wei has certain correlation with 11β-HSD1,while the reverse molec-ular docking technology can provide a feasible technical way to studycorrespondence between formulation and syndromerelation-ship.