Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols

Siddheshwar K Chauthe; Sandip B Bharate; Sudeep Sabde; Debashis Mitra; Kamlesh K Bhutani; Inder P Singh

doi:10.1016/j.bmc.2010.01.023

Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols

Bioorg Med Chem. 2010 Mar 1;18(5):2029-36. doi: 10.1016/j.bmc.2010.01.023. Epub 2010 Jan 15.

Authors

Siddheshwar K Chauthe¹, Sandip B Bharate, Sudeep Sabde, Debashis Mitra, Kamlesh K Bhutani, Inder P Singh

Affiliation

¹ Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160 062, India.

PMID: 20137956
DOI: 10.1016/j.bmc.2010.01.023

Abstract

Plants are an important source of a variety of bioactive compounds with different modes of action. Anti-HIV agents from plant sources can be useful in developing novel therapies for inhibiting HIV infection. Based on the reported anti-HIV activity of plant derived phloroglucinols, several new dimeric phloroglucinols were synthesized in the present study by varying substitution on aromatic ring and at methylene bridge. Some of the synthesized compounds have shown good HIV inhibitory activity in a human CD4+ T cell line (CEM-GFP) infected with HIV-1 NL(4.3) virus isolate. Structure-activity studies indicate that phenyl, 4-benzyloxy-1-phenyl and cyclohexyl substitution at methylene bridge gave compounds with better anti-HIV activity. Compounds 22 and 24 showed highest anti-HIV activity with an IC(50) of 0.28 microM and 2.71 microM, respectively, former was more active than the positive standard AZT in cell based assay.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / chemistry
Anti-HIV Agents / therapeutic use
Biomimetic Materials / chemical synthesis*
Biomimetic Materials / chemistry
Biomimetic Materials / therapeutic use
Dimerization
HIV Infections / drug therapy
HIV Reverse Transcriptase / antagonists & inhibitors
HIV Reverse Transcriptase / metabolism
Humans
Phloroglucinol / analogs & derivatives*
Phloroglucinol / chemical synthesis
Phloroglucinol / chemistry*
Phloroglucinol / therapeutic use
Structure-Activity Relationship
Virus Replication / drug effects

Substances

1-(3-isopentanoyl-5-((3,5-diisopentanoyl-2,4,6-trihydroxyphenyl)-4-benzyloxyphenylmethyl)-2,4,6-trihydroxyphenyl)-3-methylbutan-1-one
1-(3-isopentanoyl-5-((3,5-diisopentanoyl-2,4,6-trihydroxyphenyl)-phenylmethyl)-2,4,6-trihydroxyphenyl)-3-methylbutan-1-one
Anti-HIV Agents
Phloroglucinol
reverse transcriptase, Human immunodeficiency virus 1
HIV Reverse Transcriptase