Synthesis and evaluation on triglyceride inhibitory activities of novel indole alkaloids / 药学学报

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC50 value of 6.35 μmol·L-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

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.

Design, synthesis and anti-MRSA activities of cycloberberine derivatives with a novel chemical scaffold / 药学学报

9-Acetoxycycloberberine (1) with a unique skeleton was first identified to display a potent antimicrobial profile against methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 1-16 μg·mL-1. Taking the compound as a lead, 14 target cycloberberine analogues with diverse structures, such as berberine and chelerythrine derivatives, were synthesized and evaluated for their anti-bacterial activities. Analysis of the structure-activity relationship revealed that:① ring E was essential for the activity; ② the removing of ring B decreased the activity against MRSA. However, the antimicrobial activity against vancomycin-resistant Enterococcus faecium (VRE) was improved; ③ the introduction of a suitable rigid substituent at the 9-position was beneficial for the activity. Among them, compound 9a showed the most potential activity against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA isolates with MIC values of 0.5-1 μg·mL-1, suggesting a different mechanism from clinical drugs. It displayed higher stability in blood. Therefore, we consider 9a worthy of further investigation. The results provide key scientific evidence for development of such compounds into a new type of anti-MRSA candidates.

Study on chemical constituents of Inula cappa / 中国中药杂志

Column chromatographies over silica gel, Sephadex LH-20, reverse phase C18, and MCI, and semi-preparative HPLC were used for separation and purification of constituents from Inula cappa. The 22 compounds were obtained and their strutures were determined by NMR and MS spectra data as nine flavonoids: luteolin (1), apigenin (2), chrysoeriol (3), artemetin (4), 2', 5-di- hydroxy-3, 6, 7, 4', 5'-pentamethoxyflavone (5), chrysosplenol C (6), apigenin-5-0-β-D-glucopyranoside (7), luteolin-3-methyl, luteolin-3-methylether-4'-0-β-D-glucopyranoside (8), luteolin-4'-0-β-D-glucopyranoside (9); four triterpenes: darma-20, 24-dien- 3β-0-acetate (10), darma-20, 24-dien-3β-ol (11), epirfiedelanol (12), friedelin (13); three coumarins: scopoletin (14) , isosco- poletin (15) , scopolin(16) , and other types of compounds stigmasta-5, 22-dien-3β-0-7-one (17), stigmasterol (18), palmitic acid (19), linoleic acid (20), linoleic acid methyl ester (21), (E) -9, 12, 13-trihydroxyoetadee-10-enoie acid (22). Compound 5 is a new natural product. Compounds 3-9, 15, 17, 21, and 22 were isolated from this genus for the first time.