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dc.contributor.authorSun, Qi
dc.contributor.authorWu, Runzhi
dc.contributor.authorCai, Sutang
dc.contributor.authorLin, Yuan
dc.contributor.authorSellers, Llewlyn
dc.contributor.authorSakamoto, Kaori
dc.contributor.authorHe, Biao
dc.contributor.authorPeterson, Blake R.
dc.date.accessioned2017-04-12T15:36:48Z
dc.date.available2017-04-12T15:36:48Z
dc.date.issued2011-03-10
dc.identifier.citationSun, Q., Wu, R., Cai, S., Lin, Y., Sellers, L., Sakamoto, K., … Peterson, B. R. (2011). Synthesis and Biological Evaluation of Analogues of AKT (Protein Kinase B) Inhibitor-IV. Journal of Medicinal Chemistry, 54(5), 1126–1139. http://doi.org/10.1021/jm100912ben_US
dc.identifier.urihttp://hdl.handle.net/1808/23629
dc.description.abstractInhibitors of the PI3-kinase/AKT (protein kinase B) pathway are under investigation as anticancer and antiviral agents. The benzimidazole derivative AKT inhibitor-IV (ChemBridge 5233705) affects this pathway and exhibits potent anticancer and antiviral activity. To probe its biological activity, we synthesized AKT inhibitor-IV and 21 analogues using a novel six-step route based on ZrCl4-catalyzed cyclization of 1,2-arylenediamines with α,β-unsaturated aldehydes. We examined effects on viability of HeLa carcinoma cells, viability of normal human cells (NHBE), replication of recombinant parainfluenza virus 5 (PIV5) in HeLa cells, and replication of the intracellular bacterium Mycobacterium fortuitum in HeLa cells. Replacement of the benzimidazole N-ethyl substitutent of AKT inhibitor-IV with N-hexyl and N-dodecyl groups enhanced antiviral activity and cytotoxicity against the cancer cell line, but these compounds showed substantially lower toxicity (from 6-fold to >20-fold) against NHBE cells, and no effect on M. fortuitum, suggesting inhibition of one or more host protein(s) required for proliferation of cancer cells and PIV5. The key structural elements identified here may facilitate identification of targets of this highly biologically active scaffold.en_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jm100912b.en_US
dc.titleSynthesis and Biological Evaluation of Analogues of AKT (Protein Kinase B) Inhibitor-IVen_US
dc.typeArticleen_US
kusw.kuauthorSun, Qi
kusw.kuauthorWu, Runzhi
kusw.kuauthorCai, Sutang
kusw.kuauthorPeterson, Blake R.
kusw.kudepartmentMedicinal Chemistryen_US
dc.identifier.doi10.1021/jm100912ben_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccess


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