BIOMAT Database Logo BIOMAT Database Logo

Antitumor agents. I. DNA topoisomerase II inhibitory activity and the structural relationship of podophyllotoxin derivatives as antitumor agents. 1992

T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Hanno Research Center, Taiho Pharmaceutical Co., Ltd., Saitama, Japan.

Various podophyllotoxin derivatives from desoxypodophyllotoxin (DPT) were synthesized to examine the structural relationships between the biological significance (cytotoxic effect, effects on DNA topoisomerase II and tubulin polymerization) in vitro and antitumor activity in vivo (L 1210). An intact 6,7-methylenedioxy group of DPT is necessary to inhibit tubulin polymerization and topoisomerase II. 4'-Phenolic hydroxyl group of DPT is essential to inhibit DNA topoisomerase II and the inhibitory effect on DNA topoisomerase II contributes to a high cytotoxicity. The introduction of an aminoalkoxy group at 1-position of DPT enhances the inhibitory activity against DNA topoisomerase II and cytotoxic effect, causing the inhibitory activity against tubulin polymerization to disappear. The results of antitumor test in mice bearing L 1210 on podophyllotoxin derivatives suggest the following: 1) the strong cytotoxic effect itself is not a good indication of antitumor activity in vivo as long as it is associated with inhibition of tubulin polymerization. DNA topoisomerase II inhibitory effect contributes to an antitumor activity in vivo; 2) detailed measurements of cytotoxicity and inhibition on DNA topoisomerase II and tubulin polymerization in vitro are necessary to evaluate podophyllotoxin derivatives.

UI MeSH Term Description Entries
D007941 Leukemia P388 An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene. P388D(1) Leukemia,P388, Leukemia
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
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
D012513 Sarcoma, Experimental Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA. EHS Tumor,Sarcoma, Engelbreth-Holm-Swarm,Sarcoma, Jensen,Experimental Sarcoma,Experimental Sarcomas,Sarcomas, Experimental,Engelbreth-Holm-Swarm Sarcoma,Jensen Sarcoma,Sarcoma, Engelbreth Holm Swarm,Tumor, EHS
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
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D059005 Topoisomerase II Inhibitors Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II. DNA Gyrase Inhibitor,DNA Topoisomerase II Inhibitor,Topoisomerase 2 Inhibitors,Topoisomerase II Inhibitor,DNA Gyrase Inhibitors,DNA Topoisomerase II Inhibitors,DNA Type 2 Topoisomerase Inhibitors,Gyrase Inhibitor, DNA,Gyrase Inhibitors, DNA,II Inhibitor, Topoisomerase,Inhibitor, DNA Gyrase,Inhibitor, Topoisomerase II,Inhibitors, DNA Gyrase,Inhibitors, Topoisomerase 2,Inhibitors, Topoisomerase II

Related Publications

T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Syntheses of novel antitumor dihydroxanthone derivatives with inhibitory activity against DNA topoisomerase II.
September 1999, Bioorganic & medicinal chemistry letters,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Novel securinine derivatives as topoisomerase I based antitumor agents.
October 2016, European journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Antitumor agents. 100. Inhibition of human DNA topoisomerase II by cytotoxic ether and ester derivatives of podophyllotoxin and alpha-peltatin.
March 1989, Journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Antitumor agents, 99. Synthetic ring C aromatized podophyllotoxin analogues as potential inhibitors of human DNA topoisomerase II.
January 1988, Journal of natural products,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Antitumor agents. 78. Inhibition of human DNA topoisomerase II by podophyllotoxin and alpha-peltatin analogues.
August 1986, Journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Discovery of 1,2-diphenylethene derivatives as human DNA topoisomerase II catalytic inhibitors and antitumor agents.
December 2022, European journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Design, synthesis, and antitumor activity of novel podophyllotoxin derivatives as potent anticancer agents.
September 2013, Journal of Asian natural products research,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Inhibitory activities against topoisomerase I and II by polyhydroxybenzoyl amide derivatives and their structure-activity relationship.
April 2004, Bioorganic & medicinal chemistry letters,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents.
October 2014, European journal of medicinal chemistry,
T Terada, and K Fujimoto, and M Nomura, and J Yamashita, and T Kobunai, and S Takeda, and K Wierzba, and Y Yamada, and H Yamaguchi
Synthesis and biological evaluation of podophyllotoxin derivatives as selective antitumor agents.
July 2018, European journal of medicinal chemistry,
Copied contents to your clipboard!