Anticancer drug design based on plant-derived natural products.

This review article focuses on recent research in my laboratory on various classes of compounds that possess potent antitumor activity. These compounds were obtained by bioactivity- and mechanism of action-directed isolation and characterization coupled with rational drug design-based modification and analog synthesis. Structural modification, structure-activity relationship, and mechanism of action studies will be discussed.

[1]  M. A. Iorio.  Contraction of the tropolonic ring of colchicine by hydrogen peroxide oxidation , 1984 .

[2]  A. Brossi,et al.  Biological effects of modified colchicines. 2. Evaluation of catecholic colchicines, colchifolines, colchicide, and novel N-acyl- and N-aroyldeacetylcolchicines. , 1983, Journal of medicinal chemistry.

[3]  S. Kuo,et al.  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 Antitumor Agents , 1998 .

[4]  D. Schnur,et al.  Antitumor agents. 113. New 4 beta-arylamino derivatives of 4'-O-demethylepipodophyllotoxin and related compounds as potent inhibitors of human DNA topoisomerase II. , 1990, Journal of medicinal chemistry.

[5]  K. Lee,et al.  Antitumor agents. 141. Synthesis and biological evaluation of novel thiocolchicine analogs: N-acyl-, N-aroyl-, and N-(substituted benzyl)deacetylthiocolchicines as potent cytotoxic and antimitotic compounds. , 1993, Journal of medicinal chemistry.

[6]  B. Leyland-Jones,et al.  Teniposide: a review of 12 years of experience. , 1984, Cancer treatment reports.

[7]  N. Haim,et al.  In vitro metabolism of etoposide (VP-16-213) by liver microsomes and irreversible binding of reactive intermediates to microsomal proteins. , 1987, Biochemical pharmacology.

[8]  A. Brossi,et al.  Antitumor Agents. Part 184. Syntheses and antitubulin activity of compounds derived from reaction of thiocolchicone with amines: Lactams, alcohols, and ester analogs of allothiocolchicinoids†‡ , 1998 .

[9]  S. Hastie,et al.  Effect of the B ring and the C-7 substituent on the kinetics of colchicinoid-tubulin associations. , 1993, Biochemistry.

[10]  K. Lee,et al.  Antitumor agents. 49 tricin, kaempferol-3-O-beta-D-glucopyranoside and (+)-nortrachelogenin, antileukemic principles from Wikstroemia indica. , 1981, Journal of natural products.

[11]  Y. Nishiwaki,et al.  A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  A. Wang,et al.  The molecular structure of the complex of Hoechst 33258 and the DNA dodecamer d(CGCGAATTCGCG). , 1988, Nucleic acids research.

[13]  C. George,et al.  aS,7S‐absolute configuration of natural (−)‐colchicine and allocongeners , 1990, FEBS letters.

[14]  H. Huang,et al.  Protein tyrosine phosphatase activities are involved in apoptotic cancer cell death induced by GL331, a new homolog of etoposide. , 1996, Cancer Letters.

[15]  A. McPhail,et al.  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. , 1993, Journal of medicinal chemistry.

[16]  S. N. Timasheff,et al.  Conformational states of tubulin liganded to colchicine, tropolone methyl ether, and podophyllotoxin. , 1982, Biochemistry.

[17]  K. Paull,et al.  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. , 1993, Journal of medicinal chemistry.

[18]  C. Cheng,et al.  A common structural pattern among many biologically active compounds of natural and synthetic origin. , 1986, Medical hypotheses.

[19]  A. Brossi,et al.  Biological effects of modified colchicines. Improved preparation of 2-demethylcolchicine, 3-demethylcolchicine, and (+)-colchicine and reassignment of the position of the double bond in dehydro-7-deacetamidocolchicines. , 1981, Journal of medicinal chemistry.

[20]  G. Cragg,et al.  Metabolism of plant-derived anticancer agents. , 1988, Pharmacology & therapeutics.

[21]  H. Pinedo,et al.  Camptothecins New Anticancer Agents , 1994 .

[22]  S. Kuo,et al.  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. , 1997, Journal of medicinal chemistry.

[23]  K. Lee,et al.  Synthesis of novel water-soluble 7-(aminoacylhydrazono)-formyl camptothecins with potent inhibition of DNA topoisomerase I. , 1994, Bioorganic & medicinal chemistry.

[24]  A. Brossi,et al.  Colchicine Models: Synthesis and Binding to Tubulin of Tertamethoxybiphenyls , 1988 .

[25]  H. Pinedo,et al.  Mechanism of action of antitumor drug etoposide: a review. , 1988, Journal of the National Cancer Institute.

[26]  Y. Cheng,et al.  Antitumor agents, 107. New cytotoxic 4-alkylamino analogues of 4'-demethyl-epipodophyllotoxin as inhibitors of human DNA topoisomerase II. , 1989, Journal of natural products.

[27]  H. Stähelin,et al.  Synthesis and antimitotic activity of glycosidic lignan derivatives related to podophyllotoxin. , 1971, Journal of medicinal chemistry.

[28]  S. Cho,et al.  Antitumor agents. 194. Synthesis and biological evaluations of 4-beta-mono-, -di-, and -trisubstituted aniline-4'-O-demethyl-podophyllotoxin and related compounds with improved pharmacological profiles. , 1999, Journal of medicinal chemistry.

[29]  A. Brossi,et al.  Chapter 3 Tropolonic Colchicum Alkaloids and Allo Congeners , 1992 .

[30]  C. Myers,et al.  Irreversible binding of etoposide (VP-16-213) to deoxyribonucleic acid and proteins. , 1984, Biochemical pharmacology.

[31]  R. Dickerson,et al.  Binding of Hoechst 33258 to the minor groove of B-DNA. , 1987, Journal of molecular biology.

[32]  T. Konoshima,et al.  Antitumor agents, 154. Cytotoxic and antimitotic flavonols from Polanisia dodecandra. , 1995, Journal of Natural Products.

[33]  H. Kuga,et al.  Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. , 1991, Cancer research.

[34]  Gopal Chakrabarti,et al.  Thermodynamics of Colchicinoid-Tubulin Interactions , 1996, The Journal of Biological Chemistry.

[35]  K. Lee,et al.  Antitumor agents. 1771. Design, syntheses, and biological evaluation of novel etoposide analogs bearing pyrrolecarboxamidino group as DNA topoisomerase II inhibitors , 1997 .

[36]  K. Lee,et al.  Induction of reversible protein-linked DNA breaks in human osteogenic sarcoma cells by novel cytocidal colchicine derivatives which inhibit DNA topoisomerase II in vitro: Absence of cross-resistance in a colchicine-resistant sub-clone , 1993 .

[37]  K. J. Lee,et al.  Antitumor agents. 144. New gamma-lactone ring-modified arylamino etoposide analogs as inhibitors of human DNA topoisomerase II. , 1994, Journal of medicinal chemistry.

[38]  M. Wani,et al.  Plant antitumor agents. 23. Synthesis and antileukemic activity of camptothecin analogues. , 1986, Journal of medicinal chemistry.

[39]  S. Kuo,et al.  Antitumor agents. 178. Synthesis and biological evaluation of substituted 2-aryl-1,8-naphthyridin-4(1H)-ones as antitumor agents that inhibit tubulin polymerization. , 1997, Journal of medicinal chemistry.

[40]  A. Brossi,et al.  B ring regulation of colchicine binding kinetics and fluorescence. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[41]  S. Cho,et al.  Antitumor agents. 164. Podophenazine, 2'',3''-dichloropodophenazine, benzopodophenazine, and their 4 beta-p-nitroaniline derivatives as novel DNA topoisomerase II inhibitors. , 1996, Journal of medicinal chemistry.

[42]  D. Wylie,et al.  Metal Binding Properties of a Monoclonal Antibody Directed toward Metal-Chelate Complexes* , 1996, The Journal of Biological Chemistry.

[43]  Y. Cheng,et al.  Antitumor agents--CLXXIII. Synthesis and evaluation of camptothecin-4 beta-amino-4'-O-demethyl epipodophyllotoxin conjugates as inhibitors of mammalian DNA topoisomerases and as cytotoxic agents. , 1997, Bioorganic & medicinal chemistry.

[44]  S. Kuo,et al.  Antitumor agents. 155. Synthesis and biological evaluation of 3',6,7-substituted 2-phenyl-4-quinolones as antimicrotubule agents. , 1994, Journal of medicinal chemistry.

[45]  K. Paull,et al.  Antitumor 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone derivatives. Interactions with tubulin. , 1996, Biochemical pharmacology.

[46]  A. Brossi,et al.  Antitumor agents. 172. Synthesis and biological evaluation of novel deacetamidothiocolchicin-7-ols and ester analogs as antitubulin agents. , 1997, Journal of medicinal chemistry.

[47]  H. Sakurai,et al.  Metal- and photo-induced cleavage of DNA by podophyllotoxin, etoposide, and their related compounds. , 1991, Molecular pharmacology.

[48]  A. Rich,et al.  Binding of a Hoechst dye to d(CGCGATATCGCG) and its influence on the conformation of the DNA fragment. , 1989, Biochemistry.

[49]  R. Rava,et al.  Effect of B-ring substituents on absorption and circular dichroic spectra of colchicine analogues. , 1992, Biochemistry.

[50]  J. Flippen-Anderson,et al.  Esters of 1‐O‐Demethylthiocolchicines: Formation of Isomers in Chloroform Solution , 1985 .

[51]  H. L. Yale,et al.  Substituted 2,3-Dihydro-4(1H)-quinazolinones. A New Class of Inhibitors of Cell Multiplication. , 1967, Journal of medicinal chemistry.

[52]  S. Cho,et al.  Antitumor agents. 163. Three-dimensional quantitative structure-activity relationship study of 4'-O-demethylepipodophyllotoxin analogs using the modified CoMFA/q2-GRS approach. , 1996, Journal of medicinal chemistry.

[53]  S. Hastie,et al.  Conformational analysis of colchicinoids containing an electron-deficient aromatic ring on the B ring , 1993 .

[54]  A. McPhail,et al.  Plant Antitumor Agents. I. The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminata1,2 , 1966 .

[55]  A. Brossi,et al.  Antitumor Agents. 183. Syntheses, Conformational Analyses, and Antitubulin Activity of Allothiocolchicinoids , 1998 .

[56]  S. Kuo,et al.  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. , 1994, Journal of medicinal chemistry.

[57]  A. Brossi,et al.  Antitumor agents. 185. Synthesis and biological evaluation of tridemethylthiocolchicine analogues as novel topoisomerase II inhibitors. , 1998, Journal of medicinal chemistry.

[58]  M. Schilstra,et al.  Effects of the tubulin-colchicine complex on microtubule dynamic instability. , 1994, Biochemistry.

[59]  A. Brossi,et al.  Alfred Burger award address. Bioactive alkaloids. 4. Results of recent investigations with colchicine and physostigmine. , 1990, Journal of medicinal chemistry.

[60]  K. Lee,et al.  Synthesis and biological evaluation of tetrademethyl isocolchicine derivatives as inhibitors of DNA topoisomerase action in vitro. , 1993, Bioorganic & medicinal chemistry.