Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides.

Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides. Research Abstract Details 

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Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides. Abstract Text:

Christian P Ridley,Chaitan Khosla,

The 4-hydroxy-2-pyrone moiety is commonly observed in polyketides generated via biosynthetic engineering of type II polyketide synthases. To explore the synthetic utility of these 2-pyrones, four engineered polyketides (mutactin, SEK4, SEK15, and SEK15b) were isolated from appropriate derivatives of Streptomyces coelicolor CH999. As a test case, we prepared nine novel pyranopyrones through condensation reactions with either citral, 1-cyclohexene-carboxaldehyde, or S-perillaldehyde. Synthetic tricyclic pyranopyrones with simple aromatic substituents are known to possess anticancer properties. We therefore investigated whether pyranopyrone derivatives of aromatic polyketides exhibited bioactivity in a panel of three cancer cell lines. Pyranopyrones generated from SEK4 had activity comparable to that of H10, a pyranopyrone with a 3-pyridyl substituent, whereas other analogues were less active. These results suggest that the diverse library of carbo- and heterocycles available through the genetic engineering of type II polyketide synthases can serve as useful building blocks to generate unique bioactive molecules.

Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides. Publishing Authors By Initials

CP Ridley,C Khosla,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research

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Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: ACS chemical biology

VOLUME: 2

Page Numbers: 104-8

Journal Abbreviation: ACS Chem. Biol.

ISSN: 1554-8937

DAY: 26

MONTH: 02

YEAR: 2007

Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101282906

Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides. Keywords Mesh Terms:

KEYWORDS: Structure-Activity Relationship

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides. Information

Substance Name: Polyketide Synthases

Registry Number: 79956-01-7

Grant and Affiliation Information for Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides.

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Country: United States

AGENCY: United States NCI

GRANT: CA 77248

ACRONYM: CA

MEDLINETA: ACS Chem Biol

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