title: 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 μM. Kinase profiling of aigialomycin D against a panel of kinases has led to the identification of MNK2 as a promising target (IC50 = 0.45 μM), and preliminary structure-activity relationship studies have been carried out to identify the essential functional groups for activity.
authors.affiliation: Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology and Research (ASTAR) , 8 Biomedical Grove, Neuros #07-01, Singapore 138665 ; Department of Pharmacy, National University of Singapore , 18 Science Drive 4, Singapore 117543.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology and Research (ASTAR) , 8 Biomedical Grove, Neuros #07-01, Singapore 138665.
authors.forename: Anqi
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, National University of Singapore , 18 Science Drive 4, Singapore 117543.
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Go
authors.affiliation: Experimental Therapeutic Centre (ETC), Agency for Science, Technology and Research (ASTAR) , 31 Biopolis Way, Nanos Level 3, Singapore 138669.
authors.forename: Kassoum
authors.initials: K
authors.lastname: Nacro
authors.affiliation: Experimental Therapeutic Centre (ETC), Agency for Science, Technology and Research (ASTAR) , 31 Biopolis Way, Nanos Level 3, Singapore 138669.
authors.forename: Boping
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology and Research (ASTAR) , 8 Biomedical Grove, Neuros #07-01, Singapore 138665 ; Department of Pharmacy, National University of Singapore , 18 Science Drive 4, Singapore 117543.
authors.forename: Christina L L
authors.initials: CL
authors.lastname: Chai
keywords: Aigialomycin D; CDK2; MNK; kinase inhibitor; resorcylic acid lactone