Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591509 | Bioorganic & Medicinal Chemistry Letters | 2013 | 11 Pages |
Abstract
Novel pyrano[4,3-b]pyran-5(4H)-one based small molecules were designed as potential inhibitors of sirtuins (i.e., yeast sir2, a homolog of human SIRT1). Elegant synthesis of these compounds was performed via a multi-step sequence consisting of MCR, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of a pyran ring followed by the fused pyranone moiety and subsequent functionalization at C-8 position of the resultant core pyrano[4,3-b]pyran-5(4H)-one framework. The crystal structure analysis of a representative iodolactonized product (6d) is presented. Some of the synthesized compounds showed promising inhibitory activities when tested against yeast sir2 in vitro. The compound 6g showed dose dependent inhibition (IC50 = 78.05 μM) of yeast sir2 and good interactions with this protein in silico.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Ali Nakhi, Md. Shafiqur Rahman, Sivakumar Archana, Ravada Kishore, G.P.K. Seerapu, K. Lalith Kumar, Devyani Haldar, Manojit Pal,