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Bioorg Med Chem Lett. 2012 Feb 1;22(3):1469-74. doi: 10.1016/j.bmcl.2011.06.066. Epub 2011 Jun 22.

Synthesis and biological evaluation of deoxy-hematoxylin derivatives as a novel class of anti-HIV-1 agents.

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  • 1Molecular Imaging Medicinal Chemistry Laboratory, RIKEN Center for Molecular Imaging Science, 6-7-3 Minatoshima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.


SAR studies for the exploration a novel class of anti-human immunodeficiency virus type 1 (HIV-1) agents based on the hematoxylin structure (1) are described. The systematic deoxygenations of 1 including asymmetric synthesis were conducted to obtain a compound showing high potencies for inhibiting the nuclear import and viral replication as anti-HIV-1 agent. Among all, C-3-deoxygenated analog 16 exhibited most promising biological activities as anti-HIV-1 agent such as lower cytotoxicity (16:1; >80:40 μM), stronger inhibition of nuclear import (0.5:1.3 μM), and viral replication in HIV-1-infected TZM-bl cells (24.6:100 μM), human peripheral blood mononuclear cells (PMBCs) (30.1 μM: toxic). Different spectra of inhibitory activities against infected three healthy humans macrophages with high (donor A) and low (donor B and C) amounts of virus were also observed. Thus 16 showed 10-times stronger activity than 1 (16:1; 0.1:<1.0 μM) in the case of A, while 16 and 1 showed comparable activities in the cases of B and C (>0.01 and >0.00 1μM). The comparison of the inhibition of viral p24 antigen production was clearly indicated that compound 16 is at least twofold more potent anti-viral activity than 1. Thus, structures and actions of deoxy analogs particularly 16 could provide valuable information for the development of a novel class of anti-HIV-1 agents.

Copyright © 2011. Published by Elsevier Ltd.

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