Biomimetic synthesis of the natural product salviadione and its hybrids: discovery of tissue-specific anti-inflammatory agents for acute lung injury.

ABSTRACT: Acute lung injury (ALI) is an inflammatory disease with no effective pharmacological treatment. The therapeutic potential of the anti-inflammatory natural product tanshinone IIA (2) for ALI is seriously impaired by its poor pharmacokinetic (PK) properties. Inspired by the unique benzo[def]carbazole-3,5-dione (BCD) core of the natural product salviadione (5), a series of furan-fused BCD hybrids of 5 with 2 was rationally designed with the aim to improve both PK properties and the anti-inflammatory activity. A biomimetic synthetic approach featuring one-pot tandem N-heterocyclization was first developed for convenient assembly of salviadione (56% overall yield over 2 steps) and the designed hybrids (35-85% yields in one step). Compared to 2, most of

SUBMITTER: Ding C 

PROVIDER: S-EPMC6498537 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature