Quantitative structure-activity relationships on 5-substituted terbenzimidazoles as topoisomerase I poisons and antitumor agents

Bioorganic & Medicinal Chemistry
J S KimE J LaVoie

Abstract

Several 5-substituted terbenzimidazoles were synthesized and evaluated as mammalian topoisomerase I poisons and for cytotoxicity against a human lymphoblastoma cell line, RPMI-8402. No correlation was observed between topoisomerase I poisoning activity and the Hansch pi value or the sigma meta and sigma para values associated with each substituent. These data suggest that electronic effects and relative lipophilicity of substituents at the 5-position of these terbenzimidazoles do not have a significant effect upon intrinsic topoisomerase I poisoning activity. There was, however, a good correlation between the relative pi values for the various substituents evaluated and cytotoxic activity. Experimentally determined log P values did not correlate well with either cytotoxicity or pi values. Capacity factors (log k') as determined by high pressure liquid chromatography did correlate well with the pi values of varied substituents and cytotoxicity. These data indicate that the relative lipophilic activity of substituents at the 5-position of these terbenzimidazoles can strongly influence relative cytotoxic activity.

References

Jan 1, 1990·Advances in Pharmacology·E SchneiderL F Liu
Mar 1, 1989·European Journal of Cancer & Clinical Oncology·J CarmichaelJ B Mitchell
Jan 1, 1989·Annual Review of Biochemistry·L F Liu
Jan 1, 1985·Annual Review of Biochemistry·J C Wang
Sep 1, 1995·Journal of Medicinal Chemistry·Q SunE J LaVoie
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A Y ChenL F Liu
Jan 1, 1994·Annual Review of Pharmacology and Toxicology·A Y Chen, L F Liu
Feb 16, 1996·Journal of Medicinal Chemistry·J S KimE J LaVoie
Jan 1, 1996·Annual Review of Biochemistry·J C Wang

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Citations

Jun 24, 2003·Il Farmaco·Sabiha AlperIsmail Yalçin
Nov 25, 2000·Bioorganic & Medicinal Chemistry·M RangarajanE J Lavoie
Oct 13, 2001·Bioorganic & Medicinal Chemistry·S B Mekapati, C Hansch
Jun 21, 2008·Molecular Cancer Therapeutics·Shyamal D DesaiLeroy F Liu
Jul 23, 2002·Biological & Pharmaceutical Bulletin·Krzysztof BielawskiSławomir Wołczyński
Oct 1, 2016·Medicinal Research Reviews·Sandhya BansalVibha Tandon
Jul 15, 2000·Bioorganic & Medicinal Chemistry·M RangarajanE J LaVoie
Dec 20, 2003·Organic & Biomolecular Chemistry·Andreas SchmidtMartin Nieger
Oct 28, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·A Selcen AlpanZeki Topcu

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