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New insights into structure-activity relationship of ipomoeassin F from its bioisosteric 5-oxa/aza analogues.

ABSTRACT: Ipomoeassin F, a plant-derived macrolide, exhibited single-digit nanomolar growth inhibition activity against many cancer cell lines. In this report, a series of 5-oxa/aza analogues was prepared and screened for cytotoxicity. Replacement of 5-CH2 with O/NH simplified the synthesis and led to only a small activity loss. N-methylation almost completely restored the potency. Further studies with additional 5-oxa analogues suggested, for the first time, that size and flexibility of the ring also significantly influence the bioactivity of ipomoeassin F.

SUBMITTER: Zong G

PROVIDER: S-EPMC5800971 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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New insights into structure-activity relationship of ipomoeassin F from its bioisosteric 5-oxa/aza analogues.

Zong Guanghui G Sun Xianwei X Bhakta Rima R Whisenhunt Lucas L Hu Zhijian Z Wang Feng F Shi Wei Q WQ

European journal of medicinal chemistry 20171212

Ipomoeassin F, a plant-derived macrolide, exhibited single-digit nanomolar growth inhibition activity against many cancer cell lines. In this report, a series of 5-oxa/aza analogues was prepared and screened for cytotoxicity. Replacement of 5-CH<sub>2</sub> with O/NH simplified the synthesis and led to only a small activity loss. N-methylation almost completely restored the potency. Further studies with additional 5-oxa analogues suggested, for the first time, that size and flexibility of the ri ...[more]

PMID: 29291442

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