RIS ID

134177

Publication Details

Sansom, G. N., Kirk, N. S., Guise, C. P., Anderson, R. F., Smaill, J. B., Patterson, A. V. & Kelso, M. J. (2019). Prototyping kinase inhibitor-cytotoxin anticancer mutual prodrugs activated by tumour hypoxia: A chemical proof of concept study. Bioorganic and Medicinal Chemistry Letters, 29 (10), 1215-1219.

Abstract

Amide- and ester-linked kinase inhibitor-cytotoxin conjugates were rationally designed and synthesised as prototype hypoxia-activated anticancer mutual prodrugs. Chemical reduction of an aryl nitro trigger moiety was shown to initiate a spontaneous cyclisation/fragmentation reaction that simultaneously released the kinase inhibitor semaxanib (SU5416) and the amine- or alcohol-linked cytotoxin from the prodrugs. Preliminary cell testing and reduction potential measurements support optimisation of the compounds towards tumour-selective mutual prodrugs.

Grant Number

NHMRC/1100432

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