Inhibition of human immunodeficiency virus type 1 (HIV-1) replication by daphnodorins.
Three flavans, daphnodorins A, B and C isolated from Dahpne odora THUNB. were tested for their abilities to inhibit human immunodeficiency virus type 1 (HIV-1(IIIB)) replication in MT-4 cells. The effective concentrations (EC50) of daphnodorins A, B and C against HIV-1-induced cytolysis were 0.26 +/- 0.08, 1.8 +/- 0.6 and 3.6 +/- 0.5 micrograms/ml, respectively. Also these three compounds showed inhibitory effects of p24 antigen in human peripheral blood lymphocytes. As compared with 2',3'-dideoxycytidine 5'-triphosphate (DDC-TP), daphnodorin A and daphnodorin C had relatively weak inhibitory effects on the reverse transcriptase of HIV-1, while daphnodorin B did not show any inhibitory effect at concentrations up to 1000 micrograms/ml. These three compounds showed marked inhibitory effects on syncytium formation between HIV-1(IIIB)-infected and uninfected MOLT-4 (clone 8) cells at 3-30 micrograms/ml without inducing cytotoxicity. The concentrations of the compounds blocking syncytium formation were consistent with the effective concentrations (EC50) against HIV-induced cytolysis of MT-4 cells. These results, differing from reverse transcriptase inhibitors, suggest that the daphnodorins exert their anti-HIV-1 activity through inhibition of early events of viral replication including adsorption of the virions to the cells or the subsequent entry.
Yusa
K
K
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Oh-hara
T
T
Tsukahara
S
S
Baba
K
K
Taniguchi
M
M
Kozawa
M
M
Takeuchi
S
S
Hara
H
H
Tsuruo
T
T
D000998:Antiviral Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002459:Cell Fusion / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015726:Giant Cells / Q000187:drug effects; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D018894:Reverse Transcriptase Inhibitors; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001578:Benzopyrans; D018894:Reverse Transcriptase Inhibitors; C055028:daphnodorin B; C055027:daphnodorin A; C055029:daphnodorin C; D054303:HIV Reverse Transcriptase