KHLee-Large
Dr. Kuo-Hsiung Lee, Director, Natural Products Research Laboratories (NPRL)

The Natural Products Research Laboratories has established an exceptional research program in rational drug discovery. Current research programs in the NPRL include the following:

  1. Medicinal Chemistry
  2. Bioactive Natural Products
  3. New Anticancer and Anti-AIDS Drug Discovery and Development
  4. Chinese Medicine

Dr. Lee and his NPRL combine the fields of the most advanced natural products chemistry and synthetic medicinal chemistry as well as cutting-edge life science technologies to design and discover herbal medicine-based bioactive natural products and their analogs as clinical trials drug candidates. Since 1971, his efforts have led to the discovery of several thousand such compounds, providing leads for new generation drug design to develop future pharmaceutical agents in the same manner that numerous previously discovered bioactive natural products (including taxol, ephedrine, and artemisinin) were developed as current pharmaceutical agents to treat cancers and other diseases. The lead compounds newly discovered by Dr. Lee’s research group will provide a solid foundation of potential chemotherapeutic drug candidates in the 21st century.

 

Natural Products Research Laboratories (NPRL) Research Team, May, 2018


The Natural Products Research Laboratories (NPRL) has established an exceptional research program in rational drug discovery. Current research programs in the NPRL include the following:
  • Medicinal Chemistry
  • Bioactive Natural Products
  • New Anticancer and Anti-AIDS Drug Discovery and Development
  • Chinese Medicine
The following example products discovered by the NPRL are currently in clinical use, clinical trial, or preclinical study:
  1. PG-2 was discovered and developed by Pharmagenesis and PhytoHealth Corporation of Taiwan based on the initial advice of Dr. Lee. It is composed of polysaccharide immunostimulatory principles from Astragalus membranaceus (Huang Qi). PG-2 was approved for clinical use in treating cancer-related fatigue by the Taiwan Department of Health in 4/2011, especially for cancer patients who developed severe fatigue after receiving chemotherapy. Application for the use of PG-2 from the US FDA is ongoing.
  2. Bevirimat (DSB, PA-457, MPC-4326), derived from natural triterpenes found in Syzigium claviflorum (Pang Hua Chih Nan), was licensed previously to Panacos Pharmaceuticals, Inc. and then to Myriad Pharmaceutical Company. It succeeded in Phase IIa anti-AIDS clinical trials and notably targets a different stage of the HIV virus compared with the current anti-AIDS drugs. Bevirimat is the first member of a completely new class of HIV drug candidates called “maturation inhibitors”. Research is very actively ongoing in the NPRL aimed at producing an improved candidate compound, without a partial drug-resistant problem encountered by bevirimat during its Phase IIb clinical trials.
  3. The 2-phenyl-4-quinolone analog CVM-1118 (formerly TRX-818 or CHM-2133-P), which is related to antileukemic natural flavonoids from Wikstroemia indica (Liao Ge Wang), showed excellent in vivo antitumor activity against ovarian cancer as a result of collaborative studies with Dr. Sheng-Chu Kuo of China Medical University, Taiwan. TaiRx, Inc., (formerly Effpha Corp.), Taiwan, has licensed this technology and is currently in Phase II anticancer clinical trial in the USA.
  4. JC-9 (or ASC-9), based on the natural product curcumin from Curcuma longa rhizome (Jiang Huang) was discovered and developed in the NPRL and licensed to AndroScience Corporation. JC-9 succeeded in a Phase II clinical trial against acne and is a clinical trial candidate for prostate and other cancers.
  5. GL-331, a synthetic analog of podophyllotoxin found in Podophyllum emodi (Gui Jiu), was discovered and developed in the NPRL with co-inventorship with Dr. Yung-Chi Cheng of Yale University. The product was licensed to Genelab Technologies Inc. of CA and reached Phase II clinical trial as an anticancer drug.
  6. Neo-tanshinlactone, a natural product found in Salvia miltiorrhiza (Tanshen or Danshen), was newly discovered and synthesized by Dr. Lee’s group. Neo-tanshinlactone is more active and selective than tamoxifen, a currently used anti-breast cancer drug. Further syntheses and development of new analogs of neo-tanshinlactone as clinical trials candidates for treating breast cancer are ongoing.
  7. PBTs, novel phenanthrene-based tylophorine analogs discovered and synthesized by Dr. Lee’s group based on the natural alkaloid tylophorine isolated from Tylophora species, were found for the first time to inhibit lung cancer progression through the Slug signaling pathway resulting from a collaboration with Dr. Pan-Chyr Yang of National Taiwan University. This finding may offer a novel path of drug development to treat lung cancer.
  8. Preclinical studies on many other novel promising antiviral natural product-based leads are in progress. These include khellactone structural analogs (DCK) of the natural coumarin suksdorfin, which appears to inhibit HIV reverse transcriptase by a different mechanism from that of currently available non-nucleoside RT inhibitors. Experiments are ongoing to identify the specific molecular target. Certain structurally related pyranochromone analogs (DCP) have also shown excellent activity against both non-drug-resistant and drug-resistant HIV strains. In addition, development of novel anti-HIV diterpenes, including stelleralide A and gnidimacrin-related daphnane diterpenes to eliminate the latent HIV-1 are currently actively ongoing.

K.H. Lee’s 96 Publications in J. Med. Chem

  1. K. H. Lee, H. Furukawa, and E.S. Huang, “Antitumor Agents 3. Synthesis and Cytotoxic Activity of Helenalin Amine Adducts and Related Derivatives,” J. Med. Chem., 15, 609-611 (1972).
  2. K. H. Lee, R. Meck, C. Piantadosi, and E.S. Huang, “Antitumor Agents 4. Cytotoxicity and In Vivo Activity of Helenalin Esters and Related Derivatives,” J. Med. Chem., 16, 299-301 (1973).
  3. K. H. Lee, S.H. Kim, H. Furukawa, C. Piantadosi, and E.S. Huang, “Antitumor Agents 11. Synthesis and Cytotoxic Activity of Epoxides of Helenalin Related Derivatives,” J. Med. Chem., 18, 59-63 (1975).
  4. K. H. Lee, T. Ibuka, S.H. Kim, B.R. Vestal, I.H. Hall, and E.S. Huang, “Antitumor Agents 16. Steroidal alpha-Methylene-gamma-Lactones,” J. Med. Chem., 18, 812-817 (1975).
  5. I.H. Hall, K. H. Lee, E.C. Mar, C.O. Starnes, and T.G. Waddell, “Antitumor Agents 21. A Proposed Mechanism for Inhibition of Cancer Growth by Tenulin and Helenalin and Related Cyclopentenones,” J. Med. Chem., 20, 333-337 (1977).
  6. K. H. Lee, Y.S. Wu, and I.H. Hall, “Antitumor Agents 25. Synthesis and Antitumor Activity of Uracil and Thymine alpha-Methylene-gamma-Lactones and Related Derivatives,” J. Med. Chem., 20, 911-914 (1977).
  7. K. H. Lee, T. Ibuka, E.C. Mar, and I.H. Hall, “Antitumor Agents 31. Helenalin sym-Dimethylethylenediamine Reaction Products and Related Derivatives,” J. Med. Chem., 21, 698-701 (1978).
  8. K. H. Lee, E.C. Mar, M. Okamoto, and I.H. Hall, “Antitumor Agents 32. Synthesis and Antitumor Activity of Cyclopentenone Derivatives Related to Helenalin,” J. Med. Chem., 21, 819-822 (1978).
  9. K. H. Lee, T. Ibuka, D. Sims, O. Muraoka, H. Kiyokawa, I.H. Hall, and H.L. Kim, “Antitumor Agents 44. Bis(helenalinyl) Esters and Related Derivatives as Novel Potent Antileukemic Agents,” J. Med. Chem., 24, 924-927 (1981).
  10. S. Tani, N. Fukamiya, H. Kiyokawa, R.O. Pick, H.A. Musallam, and K. H. Lee, “Antimalarial Agents 1. alpha-Santonin-derived Cyclic Peroxide as Potential Antimalarial Agent,” J. Med. Chem., 28, 1743-1744 (1985).
  11. L.S. Thurston, H. Irie, S. Tani, F.S. Han, Z.C. Liu, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 78. Inhibition of Human DNA Topoisomerase II by Podophyllotoxin and alpha-Peltatin Analogues,” J. Med. Chem., 29, 1547-1550 (1986).
  12. K. H. Lee, G.K. Rice, I.H. Hall, and V. Amarnath, “Antitumor Agents 86. Synthesis and Cytotoxicity of alpha-Methylene-gamma-Lactone-Bearing Purines,” J. Med. Chem., 30, 586-588 (1987).
  13. T. Hayashi, F.T. Smith, and K. H. Lee, “Antitumor Agents 89. Psychorubrin, a New Cytotoxic Naphthoquinone from Psychotria rubra and Its Structure-Activity Relationships,” J. Med. Chem., 30, 2005-2008 (1987).
  14. L.S. Thurston, Y. Imakura, M. Haruna, D.H. Li, Z.C. Liu, S.Y. Liu, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 100. Inhibition of Human DNA Topoisomerase II by Cytotoxic Ether and Ester Derivatives of Podophyllotoxin and alpha-Peltatin,” J. Med. Chem., 32, 604-608 (1989).
  15. K. H. Lee, S.A. Beers, M. Mori, Z.Q. Wang, Y.H. Kuo, L. Li, S.Y. Liu, and Y.C. Cheng, “Antitumor Agents 111. New 4-Hydroxylated and 4-Halogenated Anilino Analogues of 4′-Demethylepipodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II,” J. Med. Chem., 33, 1364-1368 (1990).
  16. Z.Q. Wang, Y.H. Kuo, D. Schnur, J.P. Bowen, S.Y. Liu, F.S. Han, J.Y Chang, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 113. New 4beta-Arylamino Derivatives of 4′-Demethylepipodophyllotoxin and Related Compounds as Potent Inhibitors of Human DNA Topoisomerase II,” J. Med. Chem., 33, 2660-2666 (1990).
  17. X.M. Zhou, Z.Q. Wang, J.Y. Chang, H.X. Chen, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 120. New 4-Substituted Benzylamino and Benzyl Ether Derivatives of 4′-O-Demethylepipodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II,” J. Med. Chem., 34, 3346-3350 (1991).
  18. H. Hu, Z.Q. Wang, S.Y. Liu, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 123. Synthesis and Human DNA Topoisomerase II Inhibitory Activity of 2′-Chloro Derivatives of Etoposide and 4beta-(Arylamino)-4-O-demethylpodophyllotoxins,” J. Med. Chem., 35, 866-871 (1992).
  19. Z.Q. Wang, H. Hu, H.X. Chen, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 124. New 4beta-Substituted Aniline Derivatives of 6,7-O,O-Demethylene-4′-O-Demethylpodophyllotoxin and Related Compounds as Potent Inhibitors of Human DNA Topoisomerase II,” J. Med. Chem., 35, 871-877.
  20. H.K. Wang, J.X. Xie, J.J. Chang, K.M. Hwang, S.Y. Liu, L.M. Ballas, J.B. Jiang, and K. H. Lee, “Antitumor Agents 134. New Shiraiachrome-A- and Calphostin-C-related Perylene Derivatives as Cytotoxic and Antiviral Agents and Inhibitors of Protein Kinase C,” J. Med. Chem., 35, 2717-2721 (1992).
  21. S.C. Kuo, H.Z. Lee, J.P. Juang, Y.T. Lin, T.S. Wu, J.J. Chang, D. Lednicer, K.D. Paull, C.M. Lin, E. Hamel, and K. H. Lee, “Synthesis and Cytotoxicity of 1,6,7,8-Substituted-2-(4′-substituted phenyl)-4-quinolones and Related Compounds: Identification as Antimitotic Agents Interacting with Tubulin,” J. Med. Chem., 36, 1146-1156 (1993).
  22. L. Sun, A.T. McPhail, E. Hamel, C.M. Lin, S.B. Hastie, J.J. Chang, and K. H. Lee, “Antitumor Agents 139. Synthesis and Biological Evaluation of Thiocolchicine Analogs 5,6-Dihydro-6(S)-acyloxy- and 5,6-Dihydro-6(S)-[(aroyloxy)methyl]-1,2,3-trimethoxy-9-(methylthio)-8H-cyclohepta-[a]naphthalen-8-ones as Novel Cytotoxic and Antimitotic Agents,” J. Med. Chem., 36, 544-551 (1993).
  23. L. Sun, E. Hamel, C.M. Lin, J.J. Chang, and K. H. Lee, “Antitumor Agents 141. Synthesis and Biological Evaluation of Novel Thiocolchicine N-Acyl, N-Aroyl, and N-Substituted Benzyldeacetylthiocolchicines as Potent Cytotoxic and Antimitotic Compounds,” J. Med. Chem., 36, 1474-1479 (1993).
  24. X.M. Zhou, K.J.H. Lee, J. Cheng, S.S. Wu, H.X. Chen, X. Guo, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 144. New gamma-Lactone Ring-Modified Etoposide Analogs as Inhibitors of Human DNA Topoisomerase II,” J. Med. Chem., 37, 287-292 (1994).
  25. Y. Kashiwada, L. Huang, L.M. Ballas, J.B. Jiang, W.P. Janzen, and K. H. Lee, “New Hexahydroxybiphenyl Derivatives as Inhibitors of Protein Kinase C,” J. Med. Chem., 37, 195-200 (1994).
  26. Y.L. Zhang, X. Guo, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 148. Synthesis and Biological Evaluation of Novel 4beta-Amino Derivatives of Etoposide with Better Pharmacological Profiles,” J. Med. Chem., 37, 446-452 (1994).
  27. L. Li, H.K. Wang, S.C. Kuo, D. Lednicer, C.M. Lin, E. Hamel, and K. H. Lee, “Antitumor Agents 150. 2′,3′,4′,5′,5,6,7-Substituted 2-Phenyl-4-quinolones and Related Compounds: Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization,” J. Med. Chem., 37, 1126-1135 (1994).
  28. Y. Zhang, A. Tropsha, A.T. McPhail, and K. H. Lee, “Antitumor Agents 152. In Vitro Inhibitory Activity of Etoposide Derivative NPF Against Human Tumor Cell Lines and a Study of Its Conformation by X-Ray Crystallography, Molecular Modeling, and NMR Spectroscopy,” J. Med. Chem., 37, 1460-1464 (1994).
  29. L. Huang, Y. Kashiwada, L.M. Cosentino, S. Fan, C.H. Chen, A.T. McPhail, T. Fujioka, K. Mihashi, and K. H. Lee, “Anti-AIDS Agents 15. Synthesis and Anti-HIV Activity of Dihydroseselin-related Compounds,” J. Med. Chem., 37, 3947-3955 (1994).
  30. L. Li, H.K. Wang, S.C. Kuo, T.S. Wu, A. Mauger, C.M. Lin, E. Hamel, and K. H. Lee, “Antitumor Agents 155. Synthesis and Biological Evaluation of 3′,6,7-Substituted 2-Phenyl-4-quinolones as Antimicrotubule Agents,” J. Med. Chem., 37, 3400-3407 (1994).
  31. L. Xie, J.X. Xie, Y. Kashiwada, L.M. Cosentino, S.H. Liu, R.B. Pai, Y.C. Cheng, and K. H. Lee, “Anti-AIDS Agents 17. New Brominated Hexahydroxybiphenyl Derivatives as Potent Anti-HIV Agents,” J. Med. Chem., 38, 3003-3008 (1995).
  32. S.C. Kuo, T. Ibuka, L.J. Huang, J.C. Lien, S.R. Yean, S.C. Huang, D. Lednicer, S.L. Morris- Natschke and K. H. Lee. “Synthesis and Cytotoxicity of 1,2-Disubstituted Naphth[2,3-d]imidazole-4,9-diones and Related Compounds,” J. Med. Chem., 39, 1447-1451 (1996).
  33. S.J. Cho, A. Tropsha, M. Suffness, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 163. Three-dimensional Quantitative Structure-Activity Relationship Study of 4’-O-Demethylepipodo-phyllotoxin Analogs Using the Modified CoMFA/q2–GRS Approach,” J. Med. Chem., 39, 1383-1395 (1996).
  34. S.J. Cho, Y. Kashiwada, K.F. Bastow, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 164. Podophenazine, 2”,3”-Dichloropodophenazine, Benzopodophenazine, and Their 4beta-p-Nitroaniline Derivatives as Novel DNA Topoisomerase II Inhibitors,” J. Med. Chem., 39, 1396-1402 (1996).
  35. Y. Kashiwada, F. Hashimoto, L. M. Cosentino, C.H. Chen, and K. H. Lee, “Anti-AIDS Agents 23. Betulinic Acid and Dihydrobetulinic Acid Derivatives as Potent Anti-HIV Agents,” J. Med. Chem., 39, 1016-1017 (1996).
  36. H.K. Wang, K.F. Bastow, L.M. Cosentino, and K. H. Lee, “Antitumor Agents 166. Synthesis and Biological Evaluation of 5,6,7,8-Substituted-2-phenylthiochromen-4-ones,” J. Med. Chem., 39, 1975-1980 (1996).
  37. Q. Shi, P. Verdier-Pinard, A. Brossi, E. Hamel, A.T. McPhail, and K. H. Lee, “Antitumor Agents 172. Synthesis and Biological Evaluation of Novel Deacetamidothiocolchicin-7-ols and Ester Analogs as Antitubulin Agents,” J. Med. Chem., 40, 961-966 (1997).
  38. K. Chen, S.C. Kuo, M.C. Hsieh, A. Mauger, C.M. Lin, E. Hamel, and K. H. Lee, “Antitumor Agents 174. 2’,3’,4’,5,6,7-Substituted 2-Phenyl-1,8-naphthyridin-4-ones: Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization,” J. Med. Chem., 40, 2266-2275 (1997).
  39. K. Chen, S.C. Kuo, M.C. Hsieh, A.B. Mauger, C.M. Lin, E. Hamel, and K. H. Lee, “Antitumor Agents 178. Synthesis and Biological Evaluation of Substituted 2-Aryl-1,8-naphthyridin-4-ones as Antitumor Agents That Inhibit Tubulin Polymerization,” J. Med. Chem., 40 (19), 3049-3056 (1997).
  40. Y. Xia, Z.Y. Yang, P. Xia, K.F. Bastow, Y. Tachibana, S.C. Kuo, E. Hamel, T. Hackl, and K. H. Lee, “Antitumor Agents 181. Synthesis and Biological Evaluation of 6,7,2’,3’,4’-Substituted-1,2,3,4-Tetrahydro-2-phenyl-4-quinolones as a New Class of Antimitotic Agents,” J. Med. Chem., 41, 1155-1162 (1998).
  41. Y.H. Chao, S.C. Kuo, C.H. Wu, C.Y. Lee, A. Mauger, I.C. Sun, S.L. Morris-Natschke, and K. H. Lee, “Synthesis and Cytotoxicity of 2-Acetyl-4,8-dihydrobenzo-dithiophene-4,8-dione Derivatives,” J. Med. Chem., 41, 4658-4661 (1998).
  42. I.C. Sun, H.K. Wang, Y. Kashiwada, J.K. Shen, L.M. Cosentino, C.H. Chen, L.M. Yang, and K. H. Lee, “Anti-AIDS Agents 34. Synthesis and Structure-Activity Relationships of Betulin Derivatives as Anti-HIV Agents,” J. Med. Chem., 41, 4648-4657 (1998).
  43. X.K. Zhu, J. Guan, Y. Tachibana, K.F. Bastow, H.H. Cheng, Y.C. Cheng, and K. H. Lee, “Antitumor Agents 194. Synthesis and Biological Evaluations of 4-beta-Mono-, Di-, and Tri-substituted Aniline-4’-O-demethyl-podophyllotoxin and Related Compounds with Improved Pharmacological Profiles,” J. Med. Chem., 42, 2441-2446 (1999).
  44. S.X. Zhang, K.F. Bastow, Y. Tachibana, S.C. Kuo, E. Hamel, A. Mauger, V.L. Narayanan, and K. H. Lee, “Antitumor Agents 196. Substituted 2-Thienyl-1,8-naphthyridin-4-ones: Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization,”J. Med. Chem., 42, 4081-4087 (1999).
  45. L. Xie, Y. Takeuchi, L.M. Cosentino, and K. H. Lee, “Anti-AIDS Agents 37. Synthesis and Structure-Activity Relationships of (3’R, 4’R)-(+)-cis-Khellactone Derivatives as Novel Potent Anti-HIV Agents,” J. Med. Chem., 42, 2662-2672 (1999).
  46. S.X. Zhang, J. Feng, S.C. Kuo, A. Brossi, E. Hamel, A. Tropsha, and K. H. Lee, “Antitumor Agents 199. Three-dimensional Quantitative Structure-Activity Relationship Study of the Colchicine Binding Site Ligands Using Comparative Molecular Field Analysis,” J. Med. Chem., 43, 167-176 (2000).
  47. M.J. Hour, L.J. Huang, S.C. Kuo, Y. Xia, K. Bastow, Y. Nakanishi, E. Hamel, and K. H. Lee, “6-Alkylamino- and 2,3-Dihydro-3’-methoxy-2-phenyl-4-quinazolinones and Related Compounds: Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization,” J. Med. Chem., 43, 4479-4487 (2000).
  48. L. Xie, Y. Takeuchi, L.M. Cosentino, A.T. McPhail, and K. H. Lee, “Anti-AIDS Agents 42. Synthesis and Anti-HIV Activity of Disubstituted (3’R,4’R)-3’,4’-Di-O-(S)-camphanoyl-(+)-cis-khellactone Analogues,” J. Med. Chem., 44, 664-671 (2001).
  49. D.S. VanVliet, Y. Tachibana, K.F. Bastow, E.S. Huang, and K. H. Lee, “Antitumor Agents 207. Design, Synthesis, and Biological Testing of 4beta-Anilino-2-fluoro-4′-demethylpodophyllotoxin Analogs as Cytotoxic and Antiviral Agents,” J. Med. Chem., 44, 1422-1428 (2001).
  50. Y. Xia, Z.Y. Yang, P. Xia, T. Hackl, E. Hamel, A. Mauger, J.H. Wu, and K. H. Lee, “Antitumor Agents 211. Fluorinated 2-Phenyl-4-quinolone Derivatives as Antimitotic Antitumor Agents,”J. Med. Chem., 44, 3932-3936 (2001).
  51. Z.Y. Xiao, Y.D. Xiao, J. Feng, A. Golbraikh, A. Tropsha, and K. H. Lee, “Antitumor Agents 213. Modeling of Epipodophyllotoxin Derivatives Using Variable Selection k Nearest Neighbor QSAR Method,” J. Med. Chem., 45, 2294-2309 (2002).
  52. H. Ohtsu, Z. Xiao, J. Ishida, M. Nagai, H.K. Wang, H. Itokawa, C.Y. Su, C. Shih, T. Chiang, E. Chang, Y.F. Lee, M.Y. Tsai, C. Chang, and K. H. Lee, “Antitumor Agents 217. Curcumin Analogues as Novel Androgen Receptor Antagonists with Potentials as Anti-prostate Cancer Agents,” J. Med. Chem., 45, 5037-5042 (2002).
  53. I.C. Sun, C.H. Chen, Y. Kashiwada, J.H. Wu, H.K. Wang, and K. H. Lee, “Anti-AIDS Agents 49. Synthesis, Anti-HIV and Anti-fusion Activities of IC9564 Analogues,” J. Med. Chem., 45, 4271-4275 (2002).
  54. Y. Nakanishi, F.R. Chang, C.C. Liaw, Y.C. Wu, K.F. Bastow, and K. H. Lee, “Antitumor Agents 224. Acetogenins as Selective Inhibitors of the Human Ovarian 1A9 Tumor Cell Line,” J. Med. Chem., 46, 3185-3188 (2003).
  55. Z. Xiao, K.F. Bastow, J.R. Vance, R. Sidwell, M.S. Chen, Q. Shi and K. H. Lee, “Antitumor Agents 234. Design, Synthesis and Biological Evaluation of Novel 4β-[(4”-Benzamido)-amino]-4’-O-demethyl-epipodophyllotoxin Derivatives,” J. Med. Chem., 47, 5140-5148 (2004).
  56. X. Wang, K.F. Bastow, C.M. Sun, Y.L. Lin, H.J. Yu, M.J. Don, T.S. Wu, S. Nakamura, and K. H. Lee, “Antitumor Agents 239. Isolation, Structure Elucidation, Total Synthesis, and Anti-Breast Cancer Activity of Neo-tanshinlactone from Salvia miltiorrhiza,” J. Med. Chem., 47, 5816-5819 (2004).
  57. L. Xie, D. Yu, C. Wild, G. Allaway, and K. H. Lee, “Anti-AIDS Agents 52. Synthesis and Anti-HIV Activity of Hydroxymethyl (3’R, 4’R)-3’, 4’-Di-O-(S)-camphanoyl-(+)cis-khellactone (DCK) Derivatives,” J. Med. Chem., 47, 756-760 (2004).
  58. D. Yu, C.H. Chen, A. Brossi, and K. H. Lee, “Anti-AIDS Agents. 60. Substituted 3’R,4’R-Di-O-(-)-camphanoyl-2’,2’-dimethyldihydropyrano[2,3-f]chromone (DCP) Analogues as Potent Anti-HIV Agents, J. Med. Chem., 47, 4072-4082 (2004).
  59. D. Yu, Y. Sakurai, C.H. Chen, F.R. Chang, and K. H. Lee, “Anti-AIDS Agents 69. Moronic Acid and Other Triterpene Derivatives as Novel Potent Anti-HIV Agents,” J. Med. Chem., 49, 5462-5469 (2006).
  60. L. Lin, Q. Shi, A.K. Nyarko, K.F. Bastow, C.C. Wu, C.Y. Su, C.C.Y. Shih, and K. H. Lee, “Antitumor Agents 250. Design and Synthesis of New Curcumin Analogs as Potential Anti-prostate Cancer Agents,” J. Med. Chem., 49, 3963-3972(2006).
  61. X. Wang, K. Nakagawa-Goto, K.F. Bastow, M.J. Don, Y.L. Lin, T.S. Wu, and K. H. Lee, “Antitumor Agents 254. Synthesis and Biological Evaluation of Novel Neo-tanshinlactone Analogs as Potent Anti-breast Cancer Agents,” J. Med. Chem., 49, 5631-5634 (2006).
  62. L. Wei, Q. Shi, K.F. Bastow, A. Brossi, S.L. Morris-Natschke, K. Nakagawa-Goto, T.S. Wu, S.L. Pan, C.M. Teng, and K. H. Lee, “Antitumor Agents 253. Design, Synthesis and Antitumor Evaluation of Novel 9-Substituted Phenanthrene-based Tylophorine Derivatives as Potential Anticancer Agents,” J. Med. Chem., 50, 3674-3680 (2007).
  63. K. Nakagawa-Goto, T.H. Chen, C.Y. Peng, K.F. Bastow, J.H. Wu, and K.H. Lee, “Antitumor Agents 259. Designs, Sytheses and Structure-Activity Relationship Study of Desmosdumotin C Analogs,” J. Med. Chem., 50, 3354-3358 (2007).
  64. A.S. Lin, K. Nakagawa-Goto, F.R. Chang, D. Yu, S.L. Morris-Natschke, C.C. Wu, S.L. Chen, Y.C. Wu and K.H. Lee, “First Total Synthesis of Protoapigenone and its Analogs as Potent Cytotoxic Agents,” J. Med. Chem., 50, 3921-3927 (2007).
  65. L. Xie, H.Guo, H. Lu, X.Zhuang, A.Zhang, G.Wu, J.Ruan, T.Zhou, D.Yu, K.Qian, K.H.Lee and S.Jiang, “Development and Preclinical Studies of Broad-spectrum Anti-HIV Agent (3′R,4′R)-3-Cyanomethyl-4-methyl-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (3-Cyanomethyl-4-methyl-DCK),” J. Med. Chem., 51, 7689-7696 (2008).
  66. K. Nakagawa-Goto, K.F. Bastow, T.H. Chen, S.L. Morris-Natschke and K.H. Lee, “Antitumor Agents 260. New Desmosdumotin B Analogs with improved in Vitro Anticancer Activity,” J. Med. Chem., 51, 3297-3303 (2008).
  67. K. Qian, D. Yu, C.H. Chen, L. Huang, S.L. Morris-Natschke, T.J. Nitz, K. Salzwdedl, M. Reddick, G.P. Allaway, and K.H. Lee, “Anti-AIDS Agents 78. Design, Synthesis, Metabolic Stability Assessment, and Anti-HIV Evaluation of Novel Betulinic Acid Derivatives as Potent Anti-HIV-1 Agents,” J. Med. Chem., 52, 3248-3258 (2009).
  68. J.C. Lin, S.C. Yang, T.M. Hong, S.L. Yu, Q. Shi, L. Wei, H.Y. Chen, P.C. Yang and K.H. Lee, “Phenanthrene-Based Tylophorine-1 (PBT-1) Inhibits Lung Cancer Cell Growth through the Akt and NF-κB Pathways,” J. Med. Chem., 52, 1903-1911 (2009).
  69. Y.H. Chang, M.H. Hsu, S.H. Wang, L.J. Huang, K. Qian, S.L. Morris-Natschke, E. Hamel, S.C. Kuo, and K.H. Lee, “Design and Synthesis of 2-(3-Benzo[b]thienyl)-6,7-methylenedioxyquinolin-4-one Analogs as Potent Antitumor Agents that Inhibit Tubulin Assembly,” J. Med. Chem., 52, 4883-4891 (2009).
  70. Z. Dang, W. Lai, K. Qian, P. Ho, K.H. Lee, C.H. Chen, and L. Huang, “Betulinic Acid Derivatives as Human Immunodeficiency Virus Type 2 (HIV-2) Inhibitors,” J. Med. Chem., 52, 7887-7891 (2009).
  71. Y. Dong, Q. Shi, Y.N. Liu, X. Wang, K.F. Bastow and K.H. Lee, “Antitumor Agents 266. Design, Synthesis and Biological Evaluation of Novel 2-(Furan-2-yl)naphthalen-1-ol derivatives as Potent and Selective Anti-Breast Cancer Agents,” J. Med. Chem., 52, 3586-3590 (2009).
  72. X. Yang, Q. Shi, Y.N. Liu, K.F. Bastow, J.C. Lin, P.C. Yang and K.H. Lee, “Antitumor Agents 268. Design, Synthesis and Mechanistic Studies of New 9-Substituted Phenanthrene-based Tylophorine Analogs as Potent Cytotoxic Agents,” J. Med. Chem., 52, 5262-5268 (2009).
  73. Y. Dong, Q. Shi, H.C. Pai, C.Y. Peng, S.L. Pan, C.M. Teng, K. Nakagawa-Goto, D. Yu, Y.N. Liu, P.C. Wu, K.F. Bastow, S.L. Morris-Natschke, A. Brossi, J.Y. Lang, J. L. Hsu, M.C. Hung, E.Y.-H.P. Lee, and K.H. Lee, “Antitumor Agents 272. Structure–Activity Relationships and In Vivo Selective Anti-Breast Cancer Activity of Novel Neo-tanshinlactone Analogs,” J. Med. Chem., 53, 2299-2308 (2010).
  74. K. Qian, R.Y. Kuo, C.H. Chen, L. Huang, S.L. Morris-Natschke, and K. H. Lee, “Anti-AIDS Agents 81. Design, Synthesis and Structure-Activity Relationship Study of Betulinic Acid and Moronic Acid Derivatives as Potent HIV Maturation Inhibitors,” J. Med. Chem., 53, 3133-3141 (2010).
  75. K. Nakagawa-Goto, P.C. Chang, C.Y. Lai, , H.Y. Hung, T.H. Chen, P.C. Wu, H. Zhu, A. Sedykh, K.F. Bastow, and K.H. Lee, “Antitumor Agents 280. Multidrug Resistance-selective Desmosdumotin B Analogues,” J. Med. Chem., 53, 6699-6705 (2010).
  76. T. Zhou, Q. Shi, K.F. Bastow, and K.H. Lee, “Antitumor Agents 286. Design, Synthesis and Structure-Activity Relationship of 3’R,4’R-Disubstituted-2’,2’-dimethyldihydropyrano[2,3-f] Chromone (DSP) Analogs as Potent Chemosensitizers to Overcome Multidrug Resistance,” J. Med. Chem. 53, 8700-8708 (2010).
  77. L.C. Chou, C.T. Chen, J.C. Lee, T.D. Way, C.H. Huang, S.M. Huang, C.M. Teng, T. Yamori, T.S. Wu, C.M. Sun, D.S. Chien, K. Qian, S.L. Morris-Natschke, K.H. Lee, L.J. Huang, and S.C. Kuo, “Synthesis and Preclinical Evaluations of 2-(2-Fluorophenyl)-6,7-methylenedioxyquinolin-4-one Monosodium Phosphate (CHM-1P-Na) as a Potent Antitumor Agent,” J. Med. Chem., 53, 1616-1626 (2010).
  78. B. Qin, X. Jiang, H. Lu, X. Tian, F. Barbault, L. Huang, K. Qian, C. Chen, R. Huang, S. Jiang, K.H. Lee, and L. Xie, “Diarylaniline Derivatives as a Distinct Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors,” J. Med. Chem., 53, 4906-4916 (2010).
  79. L.C. Chou, M.T. Tsai, M.H. Hsu, S.H. Wang, T.D. Way, C.H. Huang, H.Y. Lin, K. Qian, Y.Z. Dong, K.H. Lee, L.J. Huang and S.C. Kuo, “Design, Synthesis, and Preclinical Evaluation of New 5,6-(or 6,7-)Disubstituted-2-(fluorophenyl)quinolin-4-one Derivatives as Potent Antitumor Agents,” J. Med. Chem., 53, 8047-8058 (2010).
  80. X.T. Tian, B.J. Qin, Z.Y. Wu, X.F. Wang, H. Lu, S.L. Morris-Natschke, C.H. Chen, S.B. Jiang, K.H. Lee, and L. Xie, “Design, Synthesis, and Evaluation of Diarylpyridines and Diarylanilines as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors,” J. Med. Chem., 53, 8287-8297 (2010).
  81. K. Nakagawa-Goto, P.C. Wu, C.Y. Lai, E. Hamel, H. Zhu, L. Zhang, T. Kozaka, E. Ohkoshi, M. Goto, K.F. Bastow, and K.H. Lee “Antitumor Agents 284. New Desmosdumotin-B Analogues with Bicyclic B-ring as Cytotoxic and Antitubulin Agents,” J. Med. Chem., 54, 1244-1255 (2011).
  82. X. Yang, Q. Shi, S.C. Yang, C.Y. Chen, S.L. Yu, K.F. Bastow, S.L. Morris-Natschke, P.C. Wu, C.Y. Lai, S.L. Pan, C.M. Teng, J.C. Lin, P.C. Yang and K.H. Lee, “Antitumor Agents 288. Design, Synthesis, SAR and Biological Studies of Novel Heteroatom-incorporated Antofine and Cryptopleurine Analogs as Potent and Selective Antitumor Agents,” J. Med. Chem., 54, 5097-5107 (2011).
  83. X. Yang, Q. Shi, S.C. Yang, C.Y. Chen, S.L. Yu, K.F. Bastow, S.L. Morris-Natschke, P.C. Wu, C.Y. Lai, S.L. Pan, C.M. Teng, J.C. Lin, P.C. Yang and K.H. Lee, “Antitumor Agents 288. Design, Synthesis, SAR and Biological Studies of Novel Heteroatom-incorporated Antofine and Cryptopleurine Analogs as Potent and Selective Antitumor Agents,” J. Med. Chem., 54, 5097-5107 (2011).
  84. H.Y. Hung, E. Ohkoshi, K.F. Bastow, K. Nakagawa-Goto, K.H. Lee, “Antitumor Agents 293. Non-toxic Dimethyl-4,4’-dimethoxy-5,6,5’,6’-dimethylenedioxybiphenyl-2,2’-dicarboxylate (DDB) Analogues Chemosensitize Multidrug Resistant Cancer Cells to Clinical Anticancer Drugs,” J. Med. Chem., 55, 5413-5424 (2012).
  85. L.Q. Sun, L. Zhu, K. Qian, B. Qin, L. Huang, C.H. Chen, K.H. Lee, and L. Xie, “Design, Synthesis, and Preclinical Evaluations of Novel 4-Substituted 1,5-Diarylanilines as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Drug Candidates,” J. Med. Chem., 55, 7219-7229 (2012).
  86. K. Qian, I.D. Bori, C.H. Chen, L. Huang, and K. H. Lee, “Anti-AIDS Agents 90. Novel C-28 Modified Bevirimat Analogues as Potent HIV Maturation Inhibitors,” J. Med. Chem., 55, 8128-8136 (2012).
  87. Z. Dang, P. Ho, L. Zhu, K. Qian, K.H. Lee, L. Huang, and C.H. Chen, “New Betulinic Acid Derivatives for Bevirimat-resistant Human Immunodeficiency Virus Type-1,” J. Med. Chem., 56, 2029-2037 (2013).
  88. Y. Zhao, J. Su, M. Goto, S.L. Morris-Natschke, Y. Li, Q.S. Zhao, Z.J. Yao, and K.H. Lee, “Dual-functional abeo-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-B Activation,” J. Med. Chem., 56, 4749-4757 (2013).
  89. C.Y. Chen, S.C. Yang, K.H. Lee, X. Yang, L.Y. Wei, L.P. Chow, T.C.V. Wang, T.M. Hong, J.C. Lin, C. Kuan, and P.C. Yang, “The Antitumor Agent PBT-1 Directly Targets HSP90 and hnRNP A2/B1 and Inhibits Lung Adenocarcinoma Growth and Metastasis,” J. Med. Chem., 57, 677-685 (2014).
  90. X.F. Wang, F. Guan, E. Ohkoshi, W. Guo, L. Wang, D.Q. Zhu, S.B. Wang, L.T. Wang, E. Hamel, D. Yang, L. Li, K. Qian, S.L. Morris-Natschke, S. Yuan, K.H. Lee, and L. Xie, “Optimization of 4-(N-Cycloamino)phenylquinazolines as a Novel Class of Tubulin Polymerization Inhibitors Targeting the Colchicine-binding Site,” J. Med. Chem., 57, 1390-1402 (2014).
  91. M.J. Wang, Y.Q. Liu, L.C. Chang, C.Y. Wang, Y.L. Zhao, M. Goto, X.B. Zhou, K. Qian, X. Nang, L. Yang, X.M. Yang, H.Y. Hung, S.L. Morris-Natschke, S.L. Pan, C.M. Teng, S.C. Kuo, T.S. Wu, Y.C. Wu, and K.H. Lee, “Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20(S)-Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents,” J. Med. Chem., 57, 6008-6018 (2014).
  92. K. Nakagawa-Goto, A. Oda, K.H. Lee, M. Goto, E. Hamel, “Development of a Novel Class of Tubulin Inhibitor from Desmosdumotin B with a Hydroxylated Bicyclic B-ring,” J. Med. Chem., 58, 2378-2389 (2015).
  93. 93. W. Lai, L. Huang, L. Zhu, G. Ferrari, C. Chan, W. Li, K.H. Lee, and C.H. Chen, “Gnidimacrin, a Potent Anti-HIV Diterpene, Can Eliminate Latent HIV-1 Ex Vivo by Activation of PKC Beta,” J. Med. Chem., 58, 8638-8646 (2015).
  94. Liu, L. Wei, L. Huang, F. Yu. W. Zheng, B. Win, D.W. Zhu, S. Morris-Natschke, S. Jiang, C.H. Chen, K.H. Lee, and L. Xie, “Novel HIV-1 NNRTI Agents: Optimization of Diarylanilines with High Potency against Wild-type and Rilpivirine-resistant E138K Mutant Virus,” J. Med. Chem., in press (2016).
  95. Y. Zhao, Q. Gu, S.L. Morris-Natschke, C.H. Chen, and K.H. Lee, “Incorporation of Privileged Structures into Bevirimat Can Improve Activity against Wild-type and Bevirimat-resistant HIV-1,” J. Med. Chem., in press (2016). DOI: 10.1021/acs.jmedchem.6b00461.
  96. M.T. Cui, L. Jiang, M. Goto, P.L. Hsu, L. Li, Q. Zhang, L. Wei, S.J. Yuan, E. Hamel, S.L. Morris-Natschke, K.H. Lee, and L. Xie, “In Vivo and Mechanistic Studies on Antitumor Lead 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one and Its Modification as a Novel Class of Tubulin-binding Tumor-Vasculature Disrupting Agents,” J. Med. Chem., 60, 5586-5598 (2017).

Kuo-Hsiung Lee, Ph.D.

(919) 962-0066

khlee@unc.edu

The K.H. Lee Natural Products Research Laboratories (NPRL) engage in research using medicinal chemistry-based methods to discover new drugs from herbal medicines, particularly Traditional Chinese Medicine. The NPRL combines the fields of the most advanced natural products chemistry and synthetic medicinal chemistry as well as cutting-edge life science technologies in its new drug discovery and design program. An iterative process of bioactivity screening/synthetic modification is used to optimize herbal medicine-based bioactive natural products and their analogs as clinical trials drug candidates for treating cancer and AIDS, as well as other diseases.

Masuo Goto, Ph.D.

goto@med.unc.edu

Dr. Goto’s research is centered around the mechanism of action studies on the novel natural products and their derivatives, which show selective bioactivities against cancer, especially focused on breast cancer and multidrug-resistant carcinomas.

Susan Morris-Natschke, Ph.D.

(919) 966-7771

susan_natschke@unc.edu

The Morris-Natschke laboratory focuses on natural product chemistry in collaboration with the Natural Products Research Laboratories at UNC. The goal is to support strong rational drug discovery and development research programs, particularly focusing on AIDS and cancer.

Kyoko Nakagawa-Goto, Ph.D.

(919) 883-4263

goto@email.unc.edu

Kyoko Nakagawa-Goto received her Ph.D. in Pharmaceutical Science with an emphasis in chemistry from the Graduate School of Natural Science & Technology at Kanazawa University in Japan. She worked as an Assistant Professor in the same university until 1998.

 

NPRL-Group-Luncheon
Natural Products Research Laboratories (NPRL) Research Team- NPRL Group Luncheon at The Carolina Club, February 6, 2018

 

Natural Products Research Laboratories Research Team- NPRL Group Luncheon at The Carolina Club, December 14, 2016
Natural Products Research Laboratories Research Team- NPRL Group Luncheon at The Carolina Club, December 14, 2016

 

Natural Products Research Laboratories Research Team- NPRL Group Luncheon at The Carolina Club, August 8, 2016

 

IMG_0165
Natural Products Research Laboratories Research Team- NPRL Holiday Dinner at The Carolina Club, December 10, 2015