Prevention of HIV-1 infection by phthalocyanines.
The ability of selected phthalocyanines and metallophthalocyanines to block HIV infection has been evaluated in an epithelial HeLa-CD4 cell line with an integrated LTR-beta-galactosidase gene. Sulfonated phthalocyanine itself (PcS), as well as its copper, nickel, and vanadyl chelates, were the most effective in blocking viral infection. These compounds were also very effective in blocking the fusion activity of the viral Env proteins. All of these compounds are expected to bind axial ligands weakly or not at all. In contrast, sulfonated phthalocyanines bearing metals expected to bind axial ligands more tightly (aluminum, cobalt, chromium, iron, silicon, and zinc) were less effective in blocking HIV infection and also less effective at inhibiting fusion. A number of active compounds were found to block binding of gp120 to CD4. Selected cationic and carboxy phthalocyanines, as well as porphyrazines, were also evaluated. Our results indicate that at least some of the compounds render the virus noninfectious, i.e. that they are virucidal. These compounds have potential as microbicides that might be used to provide protection against sexually transmitted HIV.
Vzorov
Andrei N
AN
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Marzilli
Luigi G
LG
Compans
Richard W
RW
Dixon
Dabney W
DW
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D000882:Haplorhini; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D008561:Membrane Fusion / Q000187:drug effects; D051379:Mice; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D007211:Indoles; D054833:Isoindoles; C013647:phthalocyanine