INHIBITION OF RETROVIRUS-INDUCED SYNCYTIUM FORMATION BY PHOTOPRODUCTSOF A BROMINATED 1,8-NAPHTHALIMIDE COMPOUND

A major disadvantage of conventional phototherapy is the requirement f or the in situ delivery of stimulating photoenergy subsequent to the b inding of photochemicals to target malignant cells, Or virus-infected cells, or viruses. This drawback has resulted in considerable limitati on in the use of photochemicals in photomedicine. To circumvent this p roblem, we have investigated the antiviral efficacy of a brominated 1, 8-naphthalimide photocompound, termed LY66Br [3-bromo-4(hexylamino)-N- hexyl-1,8-naphthalimide], which upon exposure to visible light at 420 nm generates independently of oxygen one- or more stable antiviral mol ecular photoproducts (e.g., is 'preactivated'). Human cell lines infec ted with the human immunodeficiency virus type 1 (HIV-1), or with the human T-lymphotropic virus type-1 (HTLV-I) exposed to photochemical pr oducts of LY66Br (P-LY66Br) completely lost their ability to form sync ytia in vitro. Photoproducts of P-LY66Br retain full antiviral activit y for at least 3 and 6 weeks when stored at room temperature and at -8 0 degrees C, respectively. Concentrations of P-LY66Br, effective in in hibiting syncytium formation mediated by HIV-1 and HTLV-I, were nontox ic to normal red cell components of whole blood (red blood cell 2,3-di phosphoglyceric acid, adenosine triphosphate, osmotic fragility or blo od type antigens). Additionally, no evidence of acute toxicity was dem onstrated in mice following an intravenous bolus inoculation to achiev e plasma concentration of 600 mu M of P-LY66Br. These findings represe nt the first demonstration of inhibition of retrovirus-induced syncyti um formation by a photochemical product, and justify further investiga tion of the preactivation process of photochemicals in the treatment o f systemic viral infections such as the acquired immunodeficiency synd rome (AIDS), in cancer therapy, and in sterilization of banked blood p roducts.