BIOMAT Database Logo BIOMAT Database Logo

Antitumor agents. 3. Synthesis and biological activity of 4 beta-alkyl derivatives containing hydroxy, amino, and amido groups of 4'-O-demethyl-4-desoxypodophyllotoxin as antitumor agents. 1993

T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Hanno Research Center, Taiho Pharmaceutical Co., Ltd., Saitama, Japan.

A series of 4 beta-alkyl (7-10), 4 beta-aminoalkyl (12a-y), and 4 beta-amidoalkyl derivatives (14a-g) of 4'-O-demethyl-4-desoxypodophyllotoxin have been synthesized, and their cytotoxicity, inhibition of DNA topoisomerase II (Topo II), and tubulin polymerization were evaluated. All derivatives of 12a-y and 14a-g did not inhibit tubulin polymerization. Many compounds exhibited cytotoxicity and inhibition of Topo II. In particular, 12o, 12s, 12t, and 12u strongly inhibited Topo II (IC50 (microM) 32.5, 60.9, 58.8, and 33.6, respectively) and were strong cytotoxicity against P388 cells (IC50 (M) 1.0, 4.1, 3.3, and 3.0 x 10(-9), respectively), compared with VP-16 (IC50 (microM) 59.2, IC50 (M) 1 x 10(-8), respectively). These compounds were nearly equal to or superior to VP-16 in antitumor activity in vivo (L1210, P388, and Lewis lung) and were more cytotoxic against various human cell lines in vitro than VP-16.

UI MeSH Term Description Entries
D007939 Leukemia L1210 An experimental LYMPHOCYTIC LEUKEMIA of mice. Leukemia L 1210,L 1210, Leukemia,L1210, Leukemia
D007941 Leukemia P388 An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene. P388D(1) Leukemia,P388, Leukemia
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D011034 Podophyllotoxin A lignan (LIGNANS) found in PODOPHYLLIN resin from the roots of PODOPHYLLUM plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. Epipodophyllotoxin,CPH86,Condyline,Condylox,Podocon-25,Podofilm,Podofilox,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a alpha,9 alpha))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a alpha,9 beta))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a beta,9 alpha))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a beta,8a alpha,9 beta))-Isomer,Wartec,Warticon
D005047 Etoposide A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. Demethyl Epipodophyllotoxin Ethylidine Glucoside,Celltop,Eposide,Eposin,Eto-GRY,Etomedac,Etopos,Etoposide Pierre Fabre,Etoposide Teva,Etoposide, (5S)-Isomer,Etoposide, (5a alpha)-Isomer,Etoposide, (5a alpha,9 alpha)-Isomer,Etoposide, alpha-D-Glucopyranosyl Isomer,Etoposido Ferrer Farma,Exitop,Lastet,NSC-141540,Onkoposid,Riboposid,Toposar,VP 16-213,VP-16,Vepesid,Vépéside-Sandoz,Eto GRY,Etoposide, alpha D Glucopyranosyl Isomer,NSC 141540,NSC141540,Teva, Etoposide,VP 16,VP 16 213,VP 16213,VP16,Vépéside Sandoz,alpha-D-Glucopyranosyl Isomer Etoposide
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured

Related Publications

T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Synthesis and biological evaluation of new 4β-anilino-4'-O-demethyl-4-desoxypodophyllotoxin derivatives as potential antitumor agents.
January 2011, European journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Novel carbamate derivatives of 4-beta-amino-4'-O-demethyl-4-desoxypodophyllotoxin as inhibitors of topoisomerase II: synthesis and biological evaluation.
March 2005, Organic & biomolecular chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Antitumor agents. 125. New 4 beta-benzoylamino derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin and 4 beta-benzoyl derivatives of 4'-O-demethylpodophyllotoxin as potent inhibitors of human DNA topoisomerase II.
February 1993, Pharmaceutical research,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Synthesis and evaluation of aroylthiourea derivatives of 4-β-amino-4'-O-demethyl-4-desoxypodophyllotoxin as novel topoisomerase II inhibitors.
March 2011, European journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Antitumor agents. 234. Design, synthesis, and biological evaluation of novel 4beta-[(4' '-benzamido)-amino]-4'-o-demethyl-epipodophyllotoxin derivatives.
October 2004, Journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
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.
August 1997, Bioorganic & medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Identification of Novel 4'-O-Demethyl-epipodophyllotoxin Derivatives as Antitumor Agents Targeting Topoisomerase II.
August 2022, Molecules (Basel, Switzerland),
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Synthesis and biological evaluation of Combretastatin A-4 derivatives containing a 3'-O-substituted carbonic ether moiety as potential antitumor agents.
December 2013, Chemistry Central journal,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Alkyl and carboxylalkyl esters of 4'-demethyl-4-deoxypodophyllotoxin: synthesis, cytotoxic, and antitumor activity.
February 2004, European journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and K Wierzba, and R Yamazaki, and J Shibata, and Y Sugimoto, and Y Yamada, and T Kobunai
Synthesis and biological evaluation of derivatives of 4-deoxypodophyllotoxin as antitumor agents.
September 2011, European journal of medicinal chemistry,
Copied contents to your clipboard!