Antiretroviral activity of furocoumarins plus UVA light detected by a replication-defective retrovirus.
The replication defective retrovirus, pXM5(N2), was used for an easy, safe and reproducible test for the screening of furocoumarins with antiretroviral activity. High titer viral supernatants have been photomodified by UVA light (20 kJ m-2) in the presence of different concentrations of two psolarens (8-methoxypsoralen, 8-MOP and 4,5',8-trimethylpsoralen, TMP) and one angelicin (4,6,4'-trimethylangelicin, TMA). At low concentrations (100-250 ng ml-1) 8-MOP and TMA did not show any significant antiviral activity, while TMP demonstrated a reduction of virus infectivity by one log at 250 ng ml-1. At the highest concentration (5 micrograms ml-1), TMA and TMP reduced the virus titer by one and more than two logs, respectively, being, therefore, two and four times more active than 8-MOP. The most active compound, TMP, was further tested on HIV-1 viral supernatants. Total inactivation of the HIV-1 (200 SFU) was obtained in the presence of 1 microgram ml-1 of TMP and 20 kJ m-2 of UVA light. Our results support the validity of the N2 system to detect the antiretroviral activity of furocoumarins and suggest the potential of TMP in combination with UVA light against HIV-1.
Department of Pharmaceutical Sciences, University of Padova, Italy.
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G
Miolo
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R
Tomanin
A
A
De Rossi
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F
Dall'Acqua
F
F
Zacchello
M
M
Scarpa
D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology*; D003673:Defective Viruses / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D011564:Furocoumarins / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D008730:Methoxsalen / Q000494:pharmacology; D051379:Mice; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012190:Retroviridae / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D014307:Trioxsalen / Q000494:pharmacology; D014466:Ultraviolet Rays; D014779:Virus Replication
D000998:Antiviral Agents; D003374:Coumarins; D011564:Furocoumarins; D017319:Photosensitizing Agents; C041621:4,4',6-trimethylangelicin; D008730:Methoxsalen; D014307:Trioxsalen