Design, synthesis, biological evaluation and docking study of novel indole-2-amide as anti-inflammatory agents with dual inhibition of COX and 5-LOX.

In this work, a series of novel indole-2-amide compounds were designed, synthesized, characterized and the anti-inflammatory activity in vivo were evaluated. Compounds 8a, 10b, 12h, and 12l exhibited marked anti-inflammatory activity in 2,4-Dinitrofluorobenzenethe (DNFB) - induced mice auricle edema model. Further, compounds 8a, 10b and 12h exhibited potential in vitro COX-2 inhibitory activity (IC50 = 21.86, 23.3 and 23.21 nM, respectively), while the reference drug celecoxib was 11.20 nM. The most promising compound 10b was exhibited the highest selectivity for COX-2 (selectivity index (COX-1/COX-2) = 17.45) and moderate 5-LOX inhibitory activity (IC50 = 66 nM), which comparable to positive controlled zileuton (IC50 = 38.91 nM). In addition, the test results showed compounds 10b and 12h no significant cytotoxic activity on normal cells (RAW264.7). Further, at the active sites of the COX-1, COX-2 co-crystals, 3b and 4l showed higher binding forces in the molecular docking study, which consistent with the results of in vitro experiments. These results demonstrated that these compounds had dual inhibitory activity of COX/5-LOX, providing clues for further searching for safer and more effective anti-inflammatory drugs.

Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline derivatives as potential antitumor candidate.

A novel class of tetrahydroisoquinoline derivatives was designed and synthesized as antitumor agents and evaluated for their in vitro and in vivo biological activities. The antiproliferative activities of all the target compounds on HUVEC, MCF-7, and HT-29 were evaluated. Compared with colchicine (1.04 × 10-2  µm), 17d and 17e exhibited outstanding activity on MCF-7 with IC50 values 0.26 × 10-2  µm and 0.89 × 10-3 µm in cell cytotoxicity assay. The tubulin polymerization assay demonstrated that 17d and 17e exhibited better inhibition rate. In the MCF-7-xenograft mouse model that was treated with 17d and 17e by intraperitoneal injection, the tumor weight was decreased at same rate with tamoxifen, and relative tumor proliferation rates were 59.48% and 41.33%, while tamoxifen was 45.08% with a daily dose of 20 mg/kg, which were demonstrated potent in vivo efficacy.

Design, Synthesis and Pharmacological Evaluation of Novel Piperlongumine derivatives as Potential Antiplatelet Aggregation Candidate.

A series of novel piperlongumine derivatives (4a-i, 6a-i) were designed and synthesized. The inhibitory activities of platelet aggregation induced by ADP and AA in vitro have been evaluated by bron turbidimetry and liver microsomal incubated assay. The assay results show that compounds 4e and 6e exhibited remarkable potency to that of the positive control piplartine and aspirin.

[Synthesis and biological evaluation of novel chalcone aromatic oxygen alkyl acids compounds].

Six novel ligustrazine chalcone aromatic oxygen alkyl acids compounds and two pyridine chalcone aromatic oxygen alkyl acids ester compounds were synthesized according to the traditional Chinese medicine theory removing blood stasis. The structures of target compounds were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid(AA) were measured by the liver microsomal incubation method in vitro. Hypolipidemic activities of compounds were tested in vivo for better inhibitory activities of platelet aggregation. Preliminary pharmacological results showed that compounds 7c, 8a and 11 a had potent inhibitory activity against platelet aggregation induced by AA, compounds 7c, 7d, 8a and 11 b showed significant inhibitory activity against platelet aggregation induced by ADP. Compounds 7c and 8a exhibited good hypolipidemic activities in high-fat-diet(HFD) induced hyperlipidemia C57/BL6 mice and worthy for further investigation.