Yikai Zhang

Design, synthesis, and antihepatitis B virus activities of novel 2-pyridone derivatives.

A series of novel 2-pyridone derivatives were synthesized and evaluated for their antihepatitis B virus (HBV) activity and cytotoxicity in vitro. Moderate to good activity against HBV DNA replication was observed in these 2-pyridone analogues. The most active compounds were 5d and 6l, with good inhibitory activity against HBV DNA replication (IC(50) = 0.206 and 0.12 microM, respectively) and remarkable high selectivity (selectivity indexes of >532 and 467, respectively). A pharmacophore model of the synthesized compounds was proposed by the GASP program. The pharmacophore model consists of three hydrophobic points, four HBA points, and one HBD point. The 2-pyridone derivatives represent a novel class of HBV inhibitors, which are worth further optimization.

Convenient synthesis of novel geiparvarin analogs with potential anti-cancer activity via click chemistry.

Based on the advantages of natural products in new anti-cancer drug development, we synthesized a series of novel benzopyran-4-one derivatives and evaluated their in vitro anti-cancer activities. The bioassays showed that the majority of the resultant compounds exerted anti-tumor effect against six human cancer cell lines to various extents, which supported the rationale of the design. Compound 5s exhibited highest potency of all the synthesized compounds.

Synthesis and anti-tumor activity of novel ethyl 3-aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylates.

A series of ethyl 3-aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylates were prepared through the metal-catalyzed domino reaction of alkylidene malonates and 1,4-butynediol under a one-pot reaction condition at room temperature. Their in vitro anti-proliferative activities were subsequently evaluated in A549, QGY and HeLa cells. The majority of the compounds showed potent anti-tumor activity against HeLa cells. In particular, compound 3l was the most potent compound with IC(50) value of 5.4 μM. For the first time, the X-ray structure of the anti-tumor ethyl 3-aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylates is determined.

Anti-hepatitis B virus and anti-cancer activities of novel isoflavone analogs.

We have synthesized a series of novel isoflavone analogs and evaluated their anti-HBV and anti-cancer activities in vitro. The bioassays showed that the majority of the resultant compounds exerted inhibitory effects on HBsAg and HBeAg levels, HBV DNA replication, as well as the growth of four human cancer cell lines to various extents, which supported the rationale of the design. In particular, compound 8f showed the highest activity against HBV infection and HBV-related liver cancer. Compound 7l (IC50 = 0.47 μM) also exerted remarkable inhibitory effect on the growth lung cancer cell line A-549.

Synthesis and in vitro antifungal activities of new 3-substituted benzopyrone derivatives

A series of new benzopyrone compounds were designed and synthesized and their antifungal activities in vitro were evaluated. The results showed that the benzopyrone derivatives with short terminal alkyl chain exhibited potent antifungal activity, which represent a novel class of promising leads for the development of novel non-azole antifungal agents. Compound 5j is the most potent one with MIC(80) value 1.5 μg/mL against Trichophyton rubrum. Flexible molecular docking was used to analyze the structure-activity relationships (SARs) of the compounds. The designed compounds interact with CA-CYP51 through hydrophobic and van der Waals interactions.