Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols.
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.
Chauthe
Siddheshwar K
SK
Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160 062, India.
Bharate
Sandip B
SB
Sabde
Sudeep
S
Mitra
Debashis
D
Bhutani
Kamlesh K
KK
Singh
Inder P
IP
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D019281:Dimerization; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
C549982:1-(3-isopentanoyl-5-((3,5-diisopentanoyl-2,4,6-trihydroxyphenyl)-4-benzyloxyphenylmethyl)-2,4,6-trihydroxyphenyl)-3-methylbutan-1-one; C549981:1-(3-isopentanoyl-5-((3,5-diisopentanoyl-2,4,6-trihydroxyphenyl)-phenylmethyl)-2,4,6-trihydroxyphenyl)-3-methylbutan-1-one; D019380:Anti-HIV Agents; D010696:Phloroglucinol; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase