Research

  • Design, Synthesis and Mechanism Study of Anticancer Molecules

There are three steps to study the anticancer properties of test compounds:  In vitro SAR assay, cell-based assay and in vivo assay. We have established an in vitro survival/apoptosis testing system based on detecting the cell viability and the pathways by MTT/FACS method. This system is able to screen potential chemopreventive or therapeutic agents from novel compounds. Tumor cell death and normal cell survival are detected simultaneously to develop a high activity and low toxic candidate compound.  We have completed the screening and mechanism study of indole, flavonoids and alkaloids. Here, we gave an example to illustrate this process.

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  • Design, Synthesis and Mechanism Study of Antioxidant Molecules

Antioxidants have generated considerable interest as potential therapeutic drugs against a wide variety of chronic diseases.

In the present study, the antioxidant capacity and the hepatoprotective activity of compound 1 and 2 were evaluated in chemical evaluation system, H2O2-induced PC12 cell model and CCl4-induced liver toxicity model. The results demonstrates that compound 1 and 2, two novel flavonoid derivatives, possess potential antioxidant activity and hepatoprotective effect both in vitro and in vivo. Further chemo-biological study and their enzymatic targets are ongoing in our laboratory.

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  • Synthesis and biological activity evaluation of anti-diabetes molecules

Diabetes mellitus is one of the most prevalent metabolic diseases in the world. α-Glucosidase inhibitors and dipeptidyl peptidase-IV (DPP-IV) inhibitors are two of current therapeutic approaches to treat type 2 diabetes. In the past, this lab has had initial success in structural modification of oxindoles (including tetracyclic oxindole, indirubin, isatin, indigo et al) and flavones (including flavonoid, isoflavonoid, chalcone et al) to improve their efficacy against diabetes targeting α-glucosidase and DPP-IV. We have built up enzyme-based, cell-based and animal-based assay systems of anti-diabetes in vitro and/or in vivo and computer modeling. Several potential compounds have been identified and under further investigated.

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  • Chemical Glycobiology
  1. Synthetic peptides are useful as antigens because their precise chemical definition allows one to specify the exact epitopes against which an immune response is to be raised. In our laboratory, we have previously developed self-assembled, multicomponent matrices for cell culture using a short fibrillizing peptide, Q11. Other, several bacterial sialyltransferases have been successfully employed in highly efficient one-pot multienzyme (OPME) sialylation systems for chemoenzymatic syntheses of various naturally occurring and non-natural α2−3-, α2−6-, and α2−8-linked sialosides.

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2. Synthesis of carbohydrate modified probes exploring carbohydrate-protein interactions

3. Preparation of synthetic carbohydrate vaccine against TB or tumor.

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  • Targeting drug delivery system (TDDS) for cancer treatment
  1. Application of nanocarriers used for anti-cancer drugs delivery
  2. Design and synthesis of anti-cancer drug conjugates with peptide ligands
  3. Design and synthesis of novel anti-cancer drugs by integration of ligand directed targeting and nano-technology

6 Total synthesis  and structure modification of natural flavonoids

Flavonoids are one of the most naturally occurring polyphenolic compounds. Many of them are known to display a wide variety of pharmacological activities including anti-cancer, anti-viral, antioxidant and anti-inflammatory properties. Biflavonoid, dimer of flavonoid, display a wide range of pharmacological activities. Moreover, some of them have better bioactivity than their corresponding monomers. We synthesized a series of natural flavonoids and biflavonoids by our regio-selective iodination, Suzuki coupling and other reactions. Some of them showed anti-diabetes, anti-cancer and anti-oxidant bioactivities.

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  • Funtionalization of N-heteroaromatics and application in medicinal chemistry (Dong WANG / Peng YU)

Research in our group is focused primarily upon the development of new strategies and methodologies for the synthesis of N-heteroaromatics of pharmaceutical interest.

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Representative Publications

  1. Chemosensitizing effect of Paris Saponin I on Camptothecin and 10-hydroxycamptothecin in lung cancer cells via p38 MAPK, ERK, and Akt signaling pathways. European Journal of Medicinal Chemistry. 2017, 125:760-769.
  2. 1,4-Addition Ugi Reaction Using Cyclic α,β-Unsaturated Ketone as Substrate. Organic Letters. DOI:10.1021/acs.orglett.6b02493
  3. Synthesis of Substituted Pyrroles via Copper-catalyzed Cyclization of Ethyl Allenoates with Activated Isocyanides. Chemistry – An Asian Journal. 2016, 11(15), 2121-2125.
  4. Total synthesis of 8-(6″-umbelliferyl)-apigenin and its analogs as anti-diabetic reagents. European Journal of Medicinal Chemistry. 2016, 112(21): 674-683.
  5. Inhibitory activity evaluation and mechanistic studies of tetracyclic oxindole derivatives as a-glucosidase inhibitors. European Journal of Medicinal Chemistry. 2016, 123: 365-378
  6. Paris Saponin I inhibit proliferation and promote apoptosis through down-regulating AKT activity in human non-small-cell lung cancer cells and inhibiting ERK expression in human small-cell lung cancer cells. RSC Advances. 2016, 6: 70816-70824
  7. Synthesis of multivalent difluorinated zanamivir analogs as potent antiviral inhibitors. Tetrahedron Letters. 57 (2016) 2579–258
  8. A Highly Practical and Convenient Halogenation of Fused Heterocyclic N-oxides. Tetrahedron. 2016, 72(38), 5762-5768
  9. Low toxic and high soluble camptothecin derivative e 2–47 effectively induces apoptosisof tumor cells in vitro, Biochemical and Biophysical Research Communications, 2016, 1:11-13.
  10. Synthesis and Anti-cancer Activity Evaluation of 5-(2-Carboxyethenyl)-isatin Derivatives. European Journal of Medicinal Chemistry. 2016, 112(1): 145-156.
  11. Synthesis, alpha-glucosidase inhibitory and molecular docking studies of prenylated and geranylated flavones, isoflavones and chalcones. Bioorganic & Medicinal Chemistry Letters, 2015, 25(20), 4567-4571.
  12. Total synthesis of (+/-)-Anastatins A and B. Tetrahedron Letters, 2015, 56(30), 4472-4475.
  13. Synthesis and Biological Evaluation of Novel Water-soluble poly-(ethylene glycol)-10-hydroxycamptothecin conjugates. Molecules, 2015, 20, 9393-9404.
  14. Preparation of Novel Pyrrolo[2,3-b]pyridine Derivatives via a New Concise Synthetic Approach. Bulletin of the Korean Chemical Society, 2015, 36, 1143-1147.
  15. Synthesis and antitumor activity evaluation of a novel series of xanthone derivatives. Journal of Asian Natural Products Research. 2015, 17(4): 377-383.
  16. Direct C-H iodination of 1,3-azoles catalysed by CuBr2 .Tetrahedron Letters. 2015, 56(3): 511-513.
  17. Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs. European Journal of Medicinal Chemistry, 2015, 92, 439-448.
  18. Biochemical and Biophysical Research Communications. 2014, 450 (4): 1650-1655.
  19. Concise synthesis of prenylated and geranylated chalcone natural products by regiospecific iodination and Suzuki coupling reactions. Tetrahedron Letters. 2014, 55(4): 897-899.
  20. Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents. Bioorganic & Medicinal Chemistry Letters. 2014, 24 (2), 591-594.
  21. Regioselective iodination of flavonoids by N-iodosuccinimide under neutral conditions . Tetrahedron Letters, 2013, 54(47):6345-6348.