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  • 1
    Electronic Resource
    Electronic Resource
    Anticancer drug design based on plant-derived natural products (1999)
    Springer
    Journal of biomedical science 6 (1999), S. 236-250 
    Details
    ISSN: 1423-0127
    Keywords: Anticancer agents ; Drug design ; Natural products ; Synthetic analogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253565
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  • 2
    Electronic Resource
    Electronic Resource
    Antitumor Agents 126. Novel 4β-Substituted Anilino Derivatives of 3′,4′ -O, O-Didemethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 343-350 
    Details
    ISSN: 1573-904X
    Keywords: etoposide ; DNA topoisomerase II ; anilino analogues of etoposide ; KB cells ; cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A series of derivatives of 3′,4′ 0,0-didemethylpodophyllotoxin have been synthesized and evaluated for their inhibitor activity against neoplastic cell growth (KB) and against human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results show that the compounds possessing a 4β-anilino moiety either unsubstituted or substituted at the para (F, COOCH3, COCH3, CN, CH2CN, NO2) or meta (OH) positions or with an ethylenedioxy moiety showed the same or greater activity than etoposide in causing cellular protein-linked DNA breakage and in inhibiting DNA topoisomerase II. However, compared to the corresponding 4′-0-demethyl analogues, the 3′,4′-O,O-didemethyl compounds have a similar potency in inhibition of DNA topoisomerase II but are less active in causing cellular protein-linked DNA breakage. Complete correlation between the three biological activities–cytotoxicity, inhibition of DNA topoisomerase II, and induction of protein-linked DNA breakage–was also not observed. This supports the possibility that the biological determinants of action among these compounds may be different.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018923902760
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  • 3
    Electronic Resource
    Electronic Resource
    Antitumor Agents. 125. New 4β-Benzoylamino Derivatives of 4′-O-Demethyl-4-desoxypodophyllotoxin and 4β-Benzoyl Derivatives of 4′-O-Demethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 214-219 
    Details
    ISSN: 1573-904X
    Keywords: etoposide ; DNA topoisomerase II ; amino analogues of etoposide ; KB cells ; cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A series of 4β-benzoylamino (5-17) derivatives of 4′-O-demethyl-4-desoxypodophyllotoxin and 4β-benzoyl (18-20) derivatives of 4′-O-demethyl podophyllotoxin have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 5-13 and 15-17 are more potent than etoposide in causing DNA breakage, while compounds 9, 10, 13, 14, 16, and 20 are more active than etoposide in their inhibition of the human DNA topoisomerase II. The order for the enzyme inhibitory activity of the derivatives of 4′-O-demethyl-4-desoxypodophyllotoxin is 4β-arylamino 〉 4β-benzylamino 〉 4β-benzoylamino.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018978525533
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of Helenalin and Bis(helenalinyl)malonate on Nucleic Acid and Protein Synthesis in Human KB Carcinoma Cells (1987)
    Springer
    Pharmaceutical research 4 (1987), S. 509-514 
    Details
    ISSN: 1573-904X
    Keywords: antineoplastic agents ; helenalin ; bis(helenalinyl)malonate ; KB carcinoma ; nucleic acid inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Helenalin and bis(helenalinyl)malonate were shown to be cytotoxic against the growth of human KB carcinoma cells. DNA synthesis was inhibited significantly. This inhibition was afforded because of the drugs' effects on a number of enzyme activities. The inhibition of IMP dehydrogenase and ribonucleotide reductase complex activities correlated positively with the inhibition of DNA synthesis of the KB cells. DNA polymerase activity was inhibited by the drugs to a lesser degree. The deoxyribonucleotide pools were markedly reduced in the presence of the drug, which would be consistent with a blockage of the enzyme ribonucleotide reductase as well as suppression of DNA synthesis. XMP levels were also reduced, which is consistent with suppression of IMP dehydrogenase activity by the drugs. Ribonucleoside phosphate pools, particularly CDP and GDP, were elevated after drug treatment, which would be expected with a blockage at ribonucleotide reductase. Thus DNA alkylation is not the mechanism of action of the antineoplastic sesquiterpene lactones; rather, the cell-killing effect is related to DNA synthesis inhibition by the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016435807362
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