当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Analogues of DNA minor groove cross-linking agents incorporating aminoCBI, an amino derivative of the duocarmycins: Synthesis, cytotoxicity, and potential as payloads for antibody-drug conjugates.

Analogues of DNA minor groove cross-linking agents incorporating aminoCBI, an amino derivative of the duocarmycins: Synthesis, cytotoxicity, and potential as payloads for antibody-drug conjugates.

Abstract：

:A Pd-catalysed amination method is used to convert seco-CBI, a synthetic analogue of the alkylating subunit of the duocarmycin natural products, from the phenol to amino form. This allows efficient enantioselective access to the more potent S enantiomer of aminoCBI and its incorporation into analogues of DNA minor groove cross-linking agents. Evaluation in a panel of nine human tumour cell lines shows that the bifunctional agents containing aminoCBI are generally less cytotoxic than their phenolCBI analogues and more susceptible to P-glycoprotein-mediated resistance. However, all bifunctional agents are potent cytotoxins, some in the sub-pM IC50 range, with in vitro properties that compare favourably with established microtubule-targeted ADC payloads.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Giddens AC,Lee HH,Lu GL,Miller CK,Guo J,Lewis Phillips GD,Pillow TH,Tercel M

doi

10.1016/j.bmc.2016.09.068

subject

Has Abstract

pub_date

2016-11-15 00:00:00

pages

6075-6081

issue

22

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(16)30840-9

journal_volume

24

pub_type

杂志文章

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