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Exploring aigialomycin d and its analogues as protein kinase inhibitors for cancer targets.

ABSTRACT: The natural product aigialomycin D (1) is a member of the resorcylic acid lactone (RAL) family possessing protein kinase inhibitory activities. This paper describes the synthesis of aigialomycin D and a series of its analogues and their activity for the inhibition of protein kinases related to cancer pathways. A preliminary study of these compounds in the inhibition of CDK2/cyclin A kinase has found that aigialomycin D and analogues 11 and 23 are moderate CDK2/cyclin A inhibitors with IC50 values of ca. 20 ?M. Kinase profiling of aigialomycin D against a panel of kinases has led to the identification of MNK2 as a promising target (IC50 = 0.45 ?M), and preliminary structure-activity relationship studies have been carried out to identify the essential functional groups for activity.

SUBMITTER: Xu J

PROVIDER: S-EPMC4018073 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Exploring aigialomycin d and its analogues as protein kinase inhibitors for cancer targets.

Xu Jin J Chen Anqi A Go Mei-Lin ML Nacro Kassoum K Liu Boping B Chai Christina L L CL

ACS medicinal chemistry letters 20110717 9

The natural product aigialomycin D (1) is a member of the resorcylic acid lactone (RAL) family possessing protein kinase inhibitory activities. This paper describes the synthesis of aigialomycin D and a series of its analogues and their activity for the inhibition of protein kinases related to cancer pathways. A preliminary study of these compounds in the inhibition of CDK2/cyclin A kinase has found that aigialomycin D and analogues 11 and 23 are moderate CDK2/cyclin A inhibitors with IC50 value ...[more]

PMID: 24900361

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