PLANT ANTITUMOR AGENTS

Summary

Principal Investigator: Kuo Hsiung Lee
Affiliation: University of North Carolina
Country: USA
Abstract: DESCRIPTION (verbatim from applicant's abstract): Based on continuing success and promising results in the previous grant period, the overall goal of the proposed research is to discover novel anticancer drugs from selected medicinal plants that have been chosen either for their therapeutic use to treat cancer(s) or for their novelty. Lead compounds will be isolated and identified based on cytotoxicity (human tissue culture cell line panel), mechanistic (DNA topoisomerase assays), and molecular target-based screening (androgen/androgen receptor target based assays). The identification and development of clinical trial candidates are overall goals of our program. The following specific studies will be carried out to accomplish these goals: 1) The Natural Products Laboratory (NPL) will use analytical instrumental chromatography to isolate and identify the active principles found in anticancer bioassays) termed bioactivity-directed fractionation and isolation, BDFI). The structural characterization of new active leads will be carried out by physical and spectral techniques. 2) Certain leads will be selected for structural modification and synthesis of analogs in order to elucidate their structure-activity relationships and mechanism of action as well as to improve their pharmacological profiles. Conventional structure activity relationship (SAR) studies, molecular modeling approaches, and combinatorial chemistry techniques are used by the NPL to aid lead generation and optimization. Current classes of primary interest include fluorinated phenyl quinolones, dithiophene and epipodophyllotoxin-camptothecin conjugates. 3) Promising compounds and their synthetic analogs will be submitted to the National Institutes of Health (NIH) at the National Cancer Institute (NCI) for additional in vitro and in vivo antitumor studies. Our previous program has been augmented by participation in the NCI Natural Product Repository Program (NCI-NPRP) for the study of promising cytotoxic rainforest species, and by the collaboration of Dr. C. S. Chang, University of Rochester Medical School, who has unique expertise in screening for prostate cancer targets. Our program continues to have the advantages of 1) an excellent supply of highly active lead compounds, (2) a focus on the structural modification of these new leads as clinical trials candidates, and (3) excellent productivity and a superior prospect for the successful development of a clinically useful drugs.
Funding Period: 1978-06-01 - 2005-05-31
more information: NIH RePORT

Top Publications

  1. ncbi The cytotoxic properties of natural coumarins isolated from roots of Ferulago campestris (Apiaceae) and of synthetic ester derivatives of aegelinol
    Sergio Rosselli
    Dipartimento Chimica Organica E PaternĂ², Universita di Palermo, Viale delle Scienze, Parco d Orleasn II, 90128 Palermo, Italy
    Nat Prod Commun 4:1701-6. 2009
  2. doi Antitumor agents. 261. 20(S)-protopanaxadiol and 20(s)-protopanaxatriol as antiangiogenic agents and total assignment of (1)H NMR spectra
    Yoshihide Usami
    School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599 7360, USA
    J Nat Prod 71:478-81. 2008
  3. doi Molecular mechanism of the inhibitory effect of KS-5 on bFGF-induced angiogenesis in vitro and in vivo
    Chieh Yu Peng
    Pharmacological Institute, College of Medicine, National Taiwan University, No 1, Jen Ai Road, Section 1, Taipei, Taiwan
    Cancer Lett 263:114-21. 2008
  4. ncbi Crotonkinins A and B and related diterpenoids from Croton tonkinensis as anti-inflammatory and antitumor agents
    Ping Chung Kuo
    Department of Biotechnology, National Formosa University, Yunlin, Taiwan, ROC
    J Nat Prod 70:1906-9. 2007
  5. pmc Structural analogs of tylophora alkaloids may not be functional analogs
    Wenli Gao
    Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA
    Bioorg Med Chem Lett 18:704-9. 2008
  6. ncbi Hillasides A and B, two new cytotoxic triterpene glycosides from the sea cucumber Holothuria hilla Lesson
    Jun Wu
    College of Pharmacy, Research Center for Marine Drugs, Second Military Medical University, Shanghai, China
    J Asian Nat Prod Res 9:609-15. 2007
  7. ncbi Cytotoxic ent-abietane diterpenes from Gelonium aequoreum
    Chia Lin Lee
    Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan
    Phytochemistry 69:276-87. 2008
  8. ncbi CHM-1 inhibits hepatocyte growth factor-induced invasion of SK-Hep-1 human hepatocellular carcinoma cells by suppressing matrix metalloproteinase-9 expression
    Shih Wei Wang
    Pharmacological Institute, College of Medicine, National Taiwan University, No 1, Jen Ai Road, sect 1, Taipei, Taiwan
    Cancer Lett 257:87-96. 2007
  9. ncbi Eremophilane sesquiterpenes from Ligularia macrophylla
    Qi Wang
    Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 200032, People s Republic of China
    J Nat Prod 70:1259-62. 2007
  10. pmc Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant--taxoid conjugates as novel cytotoxic agents
    Kyoko Nakagawa-Goto
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioorg Med Chem Lett 17:5204-9. 2007

Scientific Experts

  • D Colombo
  • J Koyama
  • Maurizio Bruno
  • Pei Lin Wu
  • Hui Kang Wang
  • Masayuki Horiuchi
  • Masuo Goto
  • T Akihisa
  • Kuo Hsiung Lee
  • Kenneth F Bastow
  • Kyoko Nakagawa-Goto
  • Susan L Morris-Natschke
  • Tian Shung Wu
  • Harukuni Tokuda
  • Linyi Wei
  • Chung Ren Su
  • Fang Rong Chang
  • Sheng Chu Kuo
  • Qian Shi
  • Tzu Hsuan Chen
  • Hoyoku Nishino
  • Chihiro Ito
  • Che Ming Teng
  • Po Cheng Chiang
  • Yang Chang Wu
  • Hideji Itokawa
  • Xihong Wang
  • Jin Tatsuzaki
  • Chin Chung Wu
  • Chia Lin Lee
  • Yi Nan Liu
  • Amooru G Damu
  • Chieh Yu Peng
  • Shih Wei Wang
  • Shiow Lin Pan
  • Arnold Brossi
  • Li Lin
  • Keduo Qian
  • Li Jiau Huang
  • Donglei Yu
  • Makio Shibano
  • Masahiko Taniguchi
  • Ping Chung Kuo
  • Mutsuo Kozuka
  • Yojiro Sakurai
  • Masataka Itoigawa
  • Seikou Nakamura
  • Hiroshi Furukawa
  • Nobuko Sakurai
  • Li Chen Chou
  • Chiao Ting Yen
  • Q Shi
  • Jau Chen Lin
  • Yu Hsun Chang
  • Sergio Rosselli
  • Midori Takasaki
  • Wenli Gao
  • Gang Wu
  • M Vijaya Bhaskar Reddy
  • Li Huang
  • Toshiyuki Akiyama
  • Yoshihide Usami
  • Tsung Hsiao Kuo
  • Koji Yamada
  • Jih Hwa Guh
  • Takao Yamori
  • Der Yi Huang
  • Ernest Hamel
  • Shuxing Zhang
  • Qi Wang
  • Li bo Zhou
  • Jun Wu
  • Dao Feng Chen
  • Mira M Konopleva
  • Jiu Hong Wu
  • Ching Yuan Su
  • Masafumi Horiuch
  • Charles C Y Shih
  • Cristina R Mendoza
  • Zhengrong Zou
  • Chih Chuang Liaw
  • Ya Yun Lai
  • Wan Chun Lai
  • Tsong Long Hwang
  • Du Shieng Chien
  • Tzong Der Way
  • Chung Ming Sun
  • Jang Chang Lee
  • Chi Hung Huang
  • Shih Ming Huang

Detail Information

Publications62

  1. ncbi The cytotoxic properties of natural coumarins isolated from roots of Ferulago campestris (Apiaceae) and of synthetic ester derivatives of aegelinol
    Sergio Rosselli
    Dipartimento Chimica Organica E PaternĂ², Universita di Palermo, Viale delle Scienze, Parco d Orleasn II, 90128 Palermo, Italy
    Nat Prod Commun 4:1701-6. 2009
    ..Some of them were shown to be marginally cytotoxic against the A549 lung cancer cell line...
  2. doi Antitumor agents. 261. 20(S)-protopanaxadiol and 20(s)-protopanaxatriol as antiangiogenic agents and total assignment of (1)H NMR spectra
    Yoshihide Usami
    School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599 7360, USA
    J Nat Prod 71:478-81. 2008
    ..This report is the first to completely assign the (1)H NMR signals of 2, together with correction of data for 1 from prior reports...
  3. doi Molecular mechanism of the inhibitory effect of KS-5 on bFGF-induced angiogenesis in vitro and in vivo
    Chieh Yu Peng
    Pharmacological Institute, College of Medicine, National Taiwan University, No 1, Jen Ai Road, Section 1, Taipei, Taiwan
    Cancer Lett 263:114-21. 2008
    ..In conclusion, the present study suggests that KS-5 has potential anti-angiogenetic effect for cancer therapy and other angiogenesis-dependent diseases...
  4. ncbi Crotonkinins A and B and related diterpenoids from Croton tonkinensis as anti-inflammatory and antitumor agents
    Ping Chung Kuo
    Department of Biotechnology, National Formosa University, Yunlin, Taiwan, ROC
    J Nat Prod 70:1906-9. 2007
    ..Compounds 3, 4, 6, 8, 9, and 11 had IC 50 values less than 5 microM and were more potent than the nonspecific NOS inhibitor L-NAME in inhibiting LPS-induced NO production...
  5. pmc Structural analogs of tylophora alkaloids may not be functional analogs
    Wenli Gao
    Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA
    Bioorg Med Chem Lett 18:704-9. 2008
    ..Because they do not have an identical spectrum of targets, the studied compounds are structural, but may not be functional analogs...
  6. ncbi Hillasides A and B, two new cytotoxic triterpene glycosides from the sea cucumber Holothuria hilla Lesson
    Jun Wu
    College of Pharmacy, Research Center for Marine Drugs, Second Military Medical University, Shanghai, China
    J Asian Nat Prod Res 9:609-15. 2007
    ..The two glycosides showed significant cytotoxicity against eight human tumour cell lines (A-549, MCF-7, IA9, CAKI-1, PC-3, KB, KB-VIN and HCT-8) with IC(50) in the range of 0.1-3.8 microg/ml...
  7. ncbi Cytotoxic ent-abietane diterpenes from Gelonium aequoreum
    Chia Lin Lee
    Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan
    Phytochemistry 69:276-87. 2008
    ..The isolates were evaluated for in vitro cytotoxic activity, and compounds 1 and 3 showed moderate cytotoxicity against lung (A549), breast (MDA-MB-231 and MCF7), and liver (HepG2) cancer cell lines...
  8. ncbi CHM-1 inhibits hepatocyte growth factor-induced invasion of SK-Hep-1 human hepatocellular carcinoma cells by suppressing matrix metalloproteinase-9 expression
    Shih Wei Wang
    Pharmacological Institute, College of Medicine, National Taiwan University, No 1, Jen Ai Road, sect 1, Taipei, Taiwan
    Cancer Lett 257:87-96. 2007
    ..Thus, we suggest that CHM-1 is a potential therapeutic agent against tumor invasion...
  9. ncbi Eremophilane sesquiterpenes from Ligularia macrophylla
    Qi Wang
    Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 200032, People s Republic of China
    J Nat Prod 70:1259-62. 2007
    ..The compounds were also evaluated for cytotoxic activity against human lung carcinoma (A-549) and human breast adenocarcinoma (MCF-7) and were found to show only very weak cytotoxicity...
  10. pmc Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant--taxoid conjugates as novel cytotoxic agents
    Kyoko Nakagawa-Goto
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioorg Med Chem Lett 17:5204-9. 2007
    ....
  11. ncbi Filiasparosides A-D, cytotoxic steroidal saponins from the roots of Asparagus filicinus
    Li bo Zhou
    Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 200032, People s Republic of China
    J Nat Prod 70:1263-7. 2007
    ..3-16.8 microg/mL. Compound 3 showed the most potent cytotoxicity, with EC(50) values of 2.3 and 3.0 microg/mL toward A549 and MCF-7 cell lines, respectively...
  12. pmc Anti-tumor agents 255: novel glycyrrhetinic acid-dehydrozingerone conjugates as cytotoxic agents
    Jin Tatsuzaki
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7360, USA
    Bioorg Med Chem 15:6193-9. 2007
    ..Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anti-cancer drug discovery and development...
  13. ncbi Antitumor agents 253. Design, synthesis, and antitumor evaluation of novel 9-substituted phenanthrene-based tylophorine derivatives as potential anticancer agents
    Linyi Wei
    Natural Products Research Laboratories, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Med Chem 50:3674-80. 2007
    ..Compound 24b showed modest in vivo antitumor activity against human A549 xenograft in nude mice as well as potent in vitro cytotoxic activity, and thus, is a promising anticancer lead compound...
  14. ncbi Isolation, structures, and structure - cytotoxic activity relationships of withanolides and physalins from Physalis angulata
    Amooru G Damu
    Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, Republic of China
    J Nat Prod 70:1146-52. 2007
    ..2 to 1.6 microg/mL. Structure-activity relationship analysis indicated that withanolides and physalins with 4beta-hydroxy-2-en-1-one and 5beta,6beta-epoxy moieties are potential cytotoxic agents...
  15. doi CHM-1, a novel synthetic quinolone with potent and selective antimitotic antitumor activity against human hepatocellular carcinoma in vitro and in vivo
    Shih Wei Wang
    Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
    Mol Cancer Ther 7:350-60. 2008
    ..CHM-1 is a promising chemotherapeutic agent worthy of further development into a clinical trial candidate for treating cancer, especially hepatocellular carcinoma...
  16. doi Plant-derived natural product research aimed at new drug discovery
    Hideji Itokawa
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599 7360, USA
    J Nat Med 62:263-80. 2008
    ....
  17. pmc Total synthesis of phenanthroindolizidine alkaloids (+/-)-antofine, (+/-)-deoxypergularinine, and their dehydro congeners and evaluation of their cytotoxic activity
    Chung Ren Su
    Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, ROC
    Bioorg Med Chem 16:6233-41. 2008
    ..Increasing the planarity and rigidity of the indolizidine moiety significantly reduced potency. A methoxy group at the 2-position (1a) was more favorable for cytotoxic activity than a hydrogen atom (1b)...
  18. doi Synthesis and preclinical evaluations of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-1-P-Na) as a potent antitumor agent
    Li Chen Chou
    Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan
    J Med Chem 53:1616-26. 2010
    ..With excellent antitumor activity profiles, 4 is highly promising for development as an anticancer clinical trials candidate...
  19. pmc Antitumor agents. 271: total synthesis and evaluation of brazilein and analogs as anti-inflammatory and cytotoxic agents
    Chiao Ting Yen
    Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599 7568, USA
    Bioorg Med Chem Lett 20:1037-9. 2010
    ..Additionally, 1b exhibited broad spectrum in vitro anticancer activity with IC(50) values of 6-11 microM against the four tested cancer cell lines...
  20. pmc Design and synthesis of 2-(3-benzo[b]thienyl)-6,7-methylenedioxyquinolin-4-one analogues as potent antitumor agents that inhibit tubulin assembly
    Yu Hsun Chang
    Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan
    J Med Chem 52:4883-91. 2009
    ..07 and 0.19 microM. Results from mechanism of action studies revealed that these new quinolone derivatives function as antitubulin agents...
  21. ncbi Novel anti-prostate cancer curcumin analogues that enhance androgen receptor degradation activity
    Q Shi
    AndroScience Corporation, San Diego, CA, 91121, USA
    Anticancer Agents Med Chem 9:904-12. 2009
    ..These compounds, such as ASC-J9 and its analogues (3 and 4), have now been shown to inhibit prostate cancer proliferation through a novel mechanism of enhancing AR degradation...
  22. doi Anti-HBV and cytotoxic activities of pyranocoumarin derivatives
    Chung Ren Su
    Department of Chemistry, National Cheng Kung University, Tainan, Taiwan
    Bioorg Med Chem 17:6137-43. 2009
    ..These data suggest that these three compounds could be useful hits for developing MDR-inverse drugs...
  23. pmc Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents
    Kyoko Nakagawa-Goto
    Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioorg Med Chem Lett 19:3378-81. 2009
    ..Compound 6 merits further development as a cancer preventive agent...
  24. pmc Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-kappaB pathways
    Jau Chen Lin
    Institute of Biomedical Sciences and Institute of Statistical Science, Academia Sinica, Nankang, Taipei, Taiwan
    J Med Chem 52:1903-11. 2009
    ..We conclude that PBT-1 induces cell cycle G2/M arrest and apoptosis by inactivating Akt and by inhibiting the NF-kappaB signaling pathway. PBT-1 may be a good drug candidate for anticancer chemotherapy...
  25. pmc Cytotoxic phenanthrenequinones and 9,10-dihydrophenanthrenes from Calanthe arisanensis
    Chia Lin Lee
    Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Nat Prod 72:210-3. 2009
    ..02 microg/mL). Generally, except for 7, compounds 2-11 also showed significant cytotoxic activity (EC(50) < 4 microg/mL) against some cell lines (especially PC-3 and MCF-7) in the panel...
  26. doi Cancer preventive agents. Part 8: Chemopreventive effects of stevioside and related compounds
    Midori Takasaki
    Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Chiba 288 0025, Japan
    Bioorg Med Chem 17:600-5. 2009
    ..Their activities were comparable to that of curcumin. These results suggested that 1, as well as 6 and 7, could be valuable as chemopreventive agents for chemical carcinogenesis...
  27. pmc Synthesis of unsymmetrical biphenyls as potent cytotoxic agents
    Gang Wu
    Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
    Bioorg Med Chem Lett 18:5272-6. 2008
    ....
  28. doi Design, synthesis, and biological evaluation of Mannich bases of heterocyclic chalcone analogs as cytotoxic agents
    M Vijaya Bhaskar Reddy
    Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan
    Bioorg Med Chem 16:7358-70. 2008
    ..Out of the 39 chalcones synthesized, 31 compounds showed potent activity against at least one cell line with IC(50) values ranging from 0.03 to 3.80 microg/mL. Structure-activity relationships (SAR) are also discussed...
  29. pmc Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives
    Li Huang
    Department of Surgery, Box 2926, Duke University Medical Center, Durham, NC 27710 2926, USA
    Bioorg Med Chem 16:6696-701. 2008
    ..Among the derivatives, glycyrrhetinic acid 3-O-isophthalate (17) was the most potent compound with IC(50) of 0.22microM, which was approximately 100-fold more potent than glycyrrhetinic acid...
  30. doi Antitumor agents 260. New desmosdumotin B analogues with improved in vitro anticancer activity
    Kyoko Nakagawa-Goto
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    J Med Chem 51:3297-303. 2008
    ..Thus, 1-analogues might be a new class of potent drug candidates, especially as 11 and 12 express direct selective action against tumors expressing MDR...
  31. pmc Antitumor agents 259. Design, syntheses, and structure-activity relationship study of desmosdumotin C analogs
    Kyoko Nakagawa-Goto
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Med Chem 50:3354-8. 2007
    ..2-Furyl analog 16 showed selective activity against HUVEC, suggesting that it may have potential as a new prototype for angiogenesis inhibition...
  32. pmc Antitumor agents 252. Application of validated QSAR models to database mining: discovery of novel tylophorine derivatives as potential anticancer agents
    Shuxing Zhang
    Laboratory for Molecular Modeling and Carolina Exploratory Center for Cheminformatics Research, Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Comput Aided Mol Des 21:97-112. 2007
    ..57. Our studies suggest that the approach combining validated QSAR modeling and virtual screening could be successfully used as a general tool for the discovery of novel biologically active compounds...
  33. ncbi Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds
    Masayuki Horiuchi
    Research Institute for Production Development, Sakyo ku, Kyoto 606 0805, Japan
    Nat Prod Res 20:161-6. 2006
    ..Inhibitory effect of porritoxin (1) and (2) was superior to that of beta-carotene, a well-known anti-tumor promoter. Furthermore, the structure-activity correlation of porritoxins and their related compounds were discussed...
  34. ncbi Cytotoxic activity of some natural and synthetic guaianolides
    Maurizio Bruno
    Dipartimento di Chimica Organica, Universita di Palermo, Viale delle Scienze, 90128 Palermo, Italy
    J Nat Prod 68:1042-6. 2005
    ..Repin (1) and both mono- and di-halohydrin analogues (2, 7-9, 11, 12) showed significant antitumor potency. A more effective compound (17) was obtained by esterificating repin with the paclitaxel side chain...
  35. ncbi Correlation between reduction potentials and inhibitory effects on Epstein-Barr virus activation of poly-substituted anthraquinones
    Junko Koyama
    Faculty of Pharmaceutical Sciences, Kobe Pharmaceutical University, Higashinada, Kobe 658 8558, Japan
    Cancer Lett 225:193-8. 2005
    ..It has been further shown that the correlation can be enhanced by introducing log P as an additional parameter...
  36. ncbi Novel cytotoxic monotetrahydrofuranic Annonaceous acetogenins from Annona montana
    Chih Chuang Liaw
    Graduate Institute of Natural Products, Kaohsiung Medical University, 100, Shih Chuan 1st Road, Kaohsiung, Taiwan
    Bioorg Med Chem 13:4767-76. 2005
    ..The absolute stereochemical structures of new isolates were elucidated and characterized by spectral and chemical methods. Interestingly, these compounds show special cytotoxicity against human hepatoma cells, Hep G2...
  37. ncbi Cancer preventive agents, Part 2: Synthesis and evaluation of 2-phenyl-4-quinolone and 9-oxo-9,10-dihydroacridine derivatives as novel antitumor promoters
    Seikou Nakamura
    Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioorg Med Chem 13:4396-401. 2005
    ....
  38. ncbi Intercedensides D-I, cytotoxic triterpene glycosides from the sea cucumber Mensamaria intercedens Lampert
    Zhengrong Zou
    Research Center for Marine Drugs, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai 200433, People s Republic of China
    J Nat Prod 68:540-6. 2005
    ..lntercedensides D-H (1-5) showed significant cytotoxicity (ED(50) 0.96-5.0 mug/mL) against 10 human tumor cell lines...
  39. ncbi LC/TIS-MS fingerprint profiling of Cimicifuga species and analysis of 23-Epi-26-deoxyactein in Cimicifuga racemosa commercial products
    Hui Kang Wang
    AndroScience Corporation, 11175 Flintkote Avenue, Suite F, San Diego, California 92121, USA
    J Agric Food Chem 53:1379-86. 2005
    ....
  40. ncbi Antitumor agents 243. Syntheses and cytotoxicity of desmosdumotin C derivatives
    Kyoko Nakagawa-Goto
    Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioorg Med Chem 13:2325-30. 2005
    ..Compounds 2-9, 13, and 16 were evaluated in vitro against human tumor cell replication. The 4-bromophenyl analog (2) showed potent cytotoxic activity in four different tumor cell lines...
  41. ncbi Chemical constituents of Murraya siamensis: three coumarins and their anti-tumor promoting effect
    Chihiro Ito
    Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 468 8503, Japan
    Phytochemistry 66:567-72. 2005
    ..Results of a primary screening of inhibitory effects of seven of these compounds on 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus early antigen activation in Raji cells are also presented...
  42. ncbi Antitumor-promoting activity of coumarins from citrus plants
    Chihiro Ito
    Faculty of Pharmacy, Meijo University, Tempaku, Nagoya, Japan
    Planta Med 71:84-7. 2005
    ..Osthenol (7) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test...
  43. ncbi Cancer preventive agents. Part 1: chemopreventive potential of cimigenol, cimigenol-3,15-dione, and related compounds
    Nobuko Sakurai
    Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7360, USA
    Bioorg Med Chem 13:1403-8. 2005
    ..Thus, compounds 1 and 2 exhibited not only strong antitumor-promoting activity but also significant antitumor-initiating effect on mouse skin. These data suggest that both compounds might be valuable chemopreventors...
  44. ncbi Anti-tumor-promoting activity of simple models of galactoglycerolipids with branched and unsaturated acyl chains
    Diego Colombo
    Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Universita di Milano, Via Saldini 50, 20133 Milano, Italy
    Eur J Med Chem 40:69-74. 2005
    ..Four compounds (three butenoates and one 4-methylpentanoate), when tested in the in vivo two-stage carcinogenesis test, exhibited also inhibitory effects on mouse skin tumor promotion...
  45. ncbi Synthesis and biological relationships of 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents
    Ya Yun Lai
    Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan
    Bioorg Med Chem 13:265-75. 2005
    ..The mechanism of action may be similar, but not identical, to that of tubulin binding drugs, such as navelbine and taxol. Compound 68 merits further investigation as a novel hydrophilic antimitotic agent...
  46. ncbi Correlation between reduction potentials and inhibitory effects on Epstein-Barr virus activation by emodin derivatives
    Junko Koyama
    Faculty of Pharmaceutical Sciences, Kobe Pharmaceutical University, Higashinada, Kobe 658 8558, Japan
    Cancer Lett 241:263-7. 2006
    ..The electronic properties, i.e. LUMO energy and atomic charges of carbon at the 9-position (C(9)) and oxygen at the 11-position (O(11)), may also be useful for estimating the inhibitory effect on EBV-EA activation...
  47. ncbi Cytotoxic activity of some natural and synthetic sesquiterpene lactones
    Maurizio Bruno
    Dipartimento di Chimica Organica, Universita di Palermo, Palermo, Italy
    Planta Med 71:1176-8. 2005
    ..Elemane, heliangolane and their hydroxy analogues 9 and 10, all containing an alpha,beta-unsaturated aldehyde substituent, were the most potent compounds...
  48. ncbi Antitumor agents 247. New 4-ethoxycarbonylethyl curcumin analogs as potential antiandrogenic agents
    Li Lin
    Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7360, USA
    Bioorg Med Chem 14:2527-34. 2006
    ..Among them, compound 10 was found to be the most potent anti-AR agent and is considered to be a promising drug candidate for the treatment of prostate cancer...
  49. ncbi Synthetic cinnamylphenol derivatives as cancer chemopreventive agents
    Chihiro Ito
    Faculty of Pharmacy, Meijo University, Tempaku ku, Nagoya 468 8503, Japan
    Eur J Med Chem 42:902-9. 2007
    ..These results indicate that some prenylated cinnamylphenols might be valuable as potential cancer chemopreventive agents (anti-tumor promoters)...
  50. ncbi Antitumor-promoting effects of new sesquiterpenes from Crossopetalum tonduzii
    Cristina R Mendoza
    Instituto Universitario de Bio Organica Antonio Gonzalez, Universidad de La Laguna, Avenida Astrofisico Francisco Sanchez 2, La Laguna, 38206 Tenerife
    Chem Biodivers 2:286-94. 2005
    ..The new compounds showed moderate antitumor-promoting effects with respect to the activation of the Epstein-Barr virus early antigen (EBV-EA)...
  51. pmc Dehydrozingerone, chalcone, and isoeugenol analogues as in vitro anticancer agents
    Jin Tatsuzaki
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599 7360, USA
    J Nat Prod 69:1445-9. 2006
    ..0, 1.0, and 2.0 microg/mL, respectively) and KB-VCR (IC50 values of 1.9, 1.0, and 2.0 microg/mL, respectively) cells, suggesting that they are not substrates for the P-glycoprotein drug efflux pump...
  52. ncbi Cyclic and branched acyl chain galactoglycerolipids and their effect on anti-tumor-promoting activity
    Diego Colombo
    Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Universita di Milano, Via Saldini 50, 20133 Milano, MI, Italy
    Eur J Med Chem 41:1456-63. 2006
    ....
  53. ncbi Tripfordines A-C, sesquiterpene pyridine alkaloids from Tripterygium wilfordii, and structure anti-HIV activity relationships of Tripterygium alkaloids
    Masafumi Horiuch
    Department of Interdisciplinary Studies of Natural Environment, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi hiroshima 739 8521, Japan
    J Nat Prod 69:1271-4. 2006
    ..1 microg/mL). In contrast, a hydroxy group at C-8' (carboxypropyl side chain) or C-9' (carboxybutyl side chain) was found to affect anti-HIV activity...
  54. ncbi Antitumor agents. 254. Synthesis and biological evaluation of novel neo-tanshinlactone analogues as potent anti-breast cancer agents
    Xihong Wang
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Med Chem 49:5631-4. 2006
    ..Our preliminary SAR studies showed that a methylated furan ring D and the C-4 substituent in ring A are critical for anti-breast cancer activity. Further development of 1 and 15 as anti-breast cancer drug candidates is warranted...
  55. ncbi New developments in the chemistry and biology of the bioactive constituents of Tanshen
    Xihong Wang
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Med Res Rev 27:133-48. 2007
    ..This compound might serve as a lead for developing promising antibreast cancer clinical trials candidates...
  56. ncbi Antitumor agents 251: synthesis, cytotoxic evaluation, and structure-activity relationship studies of phenanthrene-based tylophorine derivatives (PBTs) as a new class of antitumor agents
    Linyi Wei
    Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioorg Med Chem 14:6560-9. 2006
    ..16 and 0.27 microM, respectively, which are comparable to those of currently used antitumor drugs. A structure-activity relationship (SAR) study was also explored to facilitate the further development of this new compound class...
  57. pmc Antitumor agents. 250. Design and synthesis of new curcumin analogues as potential anti-prostate cancer agents
    Li Lin
    Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7360, USA
    J Med Chem 49:3963-72. 2006
    ..This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogues with better anti-prostate cancer activity...
  58. ncbi Rautandiols A and B, pterocarpans and cytotoxic constituents from Neorautanenia mitis
    Yojiro Sakurai
    Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, 27599, USA
    J Nat Prod 69:397-9. 2006
    ..Among the compounds isolated, rotenone (3) and 12-hydroxyrotenone (4) showed significant cytotoxic activity with IC(50) values of 0.008-0.010 and 0.04-0.06 microg/mL against MCF-7 and A-549 cells, respectively...
  59. ncbi Sylviside, a diterpene glucoside derivative from Gnaphalium sylvaticum
    Mira M Konopleva
    Department of Pharmacognosy and Botany, Vitebsk State University, Republic of Belarus
    J Nat Prod 69:394-6. 2006
    ..Sylviside (1) displayed weak cytotoxicity against HeLa WT (human epitheloid cervical carcinoma) cells and was also evaluated for its effects on reversing multidrug resistance in HeLa cells overexpressing MDR1...
  60. ncbi Three new agarofuran sesquiterpenes reissantins F-H from Reissantia buchananii
    Fang Rong Chang
    Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
    Planta Med 72:92-6. 2006
    ..Their structures as well as their relative stereochemistry were established on the basis of modern mass and spectroscopic methods. Compounds were assayed for cytotoxicity against HepG2 and Hep3B human liver cancer cell lines...
  61. ncbi Chalcones and other compounds from the exudates of Angelica keiskei and their cancer chemopreventive effects
    Toshihiro Akihisa
    College of Science and Technology, Nihon University, 1 8 Kanda Surugadai, Tokyo 101 8308, Japan
    J Nat Prod 69:38-42. 2006
    ..Further, isobavachalcone (4) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter...
  62. ncbi Antitumor agents. Part 236: Synthesis of water-soluble colchicine derivatives
    Kyoko Nakagawa-Goto
    Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioorg Med Chem Lett 15:235-8. 2005
    ..88 microg/mL. The thiocolchicine analogs (5, 5a) were more potent than the colchicine analogs (4, 4a) in the tubulin polymerization assay. In particular, the water-soluble salt 5a merits preclinical development as an antitumor agent...