Construction and functionalization of pyranone ring fused with pyran moiety: Design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins |
| |
Authors: | Ali Nakhi Md Shafiqur Rahman Sivakumar Archana Ravada Kishore GPK Seerapu K Lalith Kumar Devyani Haldar Manojit Pal |
| |
Institution: | 1. Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500 046, India;2. Chemical Synthesis & Process Technologies, Department of Chemistry, University of Delhi, New Delhi 110 007, India;3. Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India;4. School of Chemistry, University of Hyderabad, Gachibowli, Hyderabad 500 046, India |
| |
Abstract: | Novel pyrano4,3-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 pyrano4,3-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. |
| |
Keywords: | Pyranochromendione Pyranopyranone Iodocyclization Sirtuins |
本文献已被 ScienceDirect 等数据库收录! |
|