2 Citations (Scopus)

Abstract

In order to further explore quinoline-type structural modification of the powerful anticancer drug dolastatin 10, an Indian Ocean sea hare constituent and parent molecule of the very successful antibody drug conjugate (ADC) Adcetris, our recent quinstatin study has been extended by replacing the quinoline ring with an isoquinoline. The resulting isoquinstatins (4-6) were modified to N-terminal desmethylisoquinstatins (7-9) and, in turn, bonded to appropriate linker units to give linker-desmethylisoquinstatin conjugates 11-13 in preparation for eventual monoclonal antibody attachment. Comparison of the new isoquinstatins with their quinstatin counterparts against six human cancer cell lines indicated the isoquinstatins to have GI50 values that were comparable to or somewhat higher than those of the isomeric quinstatins. However, desmethylisoquinstatin 5 (7) was significantly more potent than its desmethylquinstatin 5 analogue. When evaluated against quinstatin 8, its isoquinstatin 8 (6) counterpart was somewhat less potent. In general, the isoquinstatins evaluated proved to be quite strong cancer cell growth inhibitors.

Original languageEnglish (US)
Pages (from-to)451-457
Number of pages7
JournalJournal of Natural Products
Volume81
Issue number3
DOIs
StatePublished - Mar 23 2018

Fingerprint

dolastatin 10
Antineoplastic Agents
Hares
Indian Ocean
Growth Inhibitors
Oceans and Seas
Pharmaceutical Preparations
Neoplasms
Monoclonal Antibodies
Cells
Cell Line
Molecules
Antibodies
quinoline
isoquinoline
cAC10-vcMMAE

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

Antineoplastic Agents. 605. Isoquinstatins. / Pettit, George; Melody, Noeleen; Chapuis, Jean.

In: Journal of Natural Products, Vol. 81, No. 3, 23.03.2018, p. 451-457.

Research output: Contribution to journalArticle

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