Literature DB >> 20303263

Novel benzofuran-3-one indole inhibitors of PI3 kinase-alpha and the mammalian target of rapamycin: hit to lead studies.

Matthew G Bursavich1, Natasja Brooijmans, Lawrence Feldberg, Irwin Hollander, Stephen Kim, Sabrina Lombardi, Kaapjoo Park, Robert Mallon, Adam M Gilbert.   

Abstract

A series of benzofuran-3-one indole phosphatidylinositol-3-kinases (PI3K) inhibitors identified via HTS has been prepared. The optimized inhibitors possess single digit nanomolar activity against p110alpha (PI3K-alpha), good pharmaceutical properties, selectivity versus p110gamma (PI3K-gamma), and tunable selectivity versus the mammalian target of rapamycin (mTOR). Modeling of compounds 9 and 32 in homology models of PI3K-alpha and mTOR supports the proposed rationale for selectivity. Compounds show activity in multiple cellular proliferation assays with signaling through the PI3K pathway confirmed via phospho-Akt inhibition in PC-3 cells. Copyright 2010 Elsevier Ltd. All rights reserved.

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Year:  2010        PMID： 20303263     DOI： 10.1016/j.bmcl.2010.02.082

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  6 in total

Review 1.  Targeted regulation of PI3K/Akt/mTOR/NF-κB signaling by indole compounds and their derivatives: mechanistic details and biological implications for cancer therapy.

Authors:  Aamir Ahmad; Bernhard Biersack; Yiwei Li; Dejuan Kong; Bin Bao; Rainer Schobert; Subhash B Padhye; Fazlul H Sarkar
Journal:  Anticancer Agents Med Chem       Date:  2013-09       Impact factor: 2.505

2.  Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study.

Authors:  Omar A El-Khouly; Morkos A Henen; Magda A-A El-Sayed; Mona I Shabaan; Shahenda M El-Messery
Journal:  Bioorg Med Chem       Date:  2020-12-27       Impact factor: 3.641

3.  Thiazolidinedione-based PI3Kα inhibitors: an analysis of biochemical and virtual screening methods.

Authors:  Jo-Anne Pinson; Oleg Schmidt-Kittler; Jiuxiang Zhu; Ian G Jennings; Kenneth W Kinzler; Bert Vogelstein; David K Chalmers; Philip E Thompson
Journal:  ChemMedChem       Date:  2011-01-04       Impact factor: 3.466

4.  Semisynthetic aurones inhibit tubulin polymerization at the colchicine-binding site and repress PC-3 tumor xenografts in nude mice and myc-induced T-ALL in zebrafish.

Authors:  Yanqi Xie; Liliia M Kril; Tianxin Yu; Wen Zhang; Mykhaylo S Frasinyuk; Svitlana P Bondarenko; Kostyantyn M Kondratyuk; Elizabeth Hausman; Zachary M Martin; Przemyslaw P Wyrebek; Xifu Liu; Agripina Deaciuc; Linda P Dwoskin; Jing Chen; Haining Zhu; Chang-Guo Zhan; Vitaliy M Sviripa; Jessica Blackburn; David S Watt; Chunming Liu
Journal:  Sci Rep       Date:  2019-04-23       Impact factor: 4.379

5.  Design, synthesis and computational study of new benzofuran hybrids as dual PI3K/VEGFR2 inhibitors targeting cancer.

Authors:  Omar A El-Khouly; Morkos A Henen; Magda A-A El-Sayed; Shahenda M El-Messery
Journal:  Sci Rep       Date:  2022-10-12       Impact factor: 4.996

6.  Synthesis and in vitro inhibition effect of new pyrido[2,3-d]pyrimidine derivatives on erythrocyte carbonic anhydrase I and II.

Authors:  Hilal Kuday; Fatih Sonmez; Cigdem Bilen; Emre Yavuz; Nahit Gençer; Mustafa Kucukislamoglu
Journal:  Biomed Res Int       Date:  2014-08-04       Impact factor: 3.411
  6 in total

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