Chanh T C, Lewis D E, Judy M M, Sogandares-Bernal F, Michalek G R, Utecht R E, Skiles H, Chang S C, Matthews J L
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78228.
Antiviral Res. 1994 Oct;25(2):133-46. doi: 10.1016/0166-3542(94)90102-3.
A major disadvantage of conventional phototherapy is the requirement for the in situ delivery of stimulating photoenergy subsequent to the binding of photochemicals to target malignant cells, or virus-infected cells, or viruses. This drawback has resulted in considerable limitation in the use of photochemicals in photomedicine. To circumvent this problem, 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 molecular photoproducts (e.g., is 'preactivated'). Human cell lines infected with the human immunodeficiency virus type 1 (HIV-1), or with the human T-lymphotropic virus type-1 (HTLV-I) exposed to photochemical products of LY66Br (P-LY66Br) completely lost their ability to form syncytia in vitro. Photoproducts of P-LY66Br retain full antiviral activity for at least 3 and 6 weeks when stored at room temperature and at -80 degrees C, respectively. Concentrations of P-LY66Br, effective in inhibiting syncytium formation mediated by HIV-1 and HTLV-I, were nontoxic to normal red cell components of whole blood (red blood cell 2,3-diphosphoglyceric acid, adenosine triphosphate, osmotic fragility or blood type antigens). Additionally, no evidence of acute toxicity was demonstrated in mice following an intravenous bolus inoculation to achieve plasma concentration of 600 microM of P-LY66Br. These findings represent the first demonstration of inhibition of retrovirus-induced syncytium formation by a photochemical product, and justify further investigation of the preactivation process of photochemicals in the treatment of systemic viral infections such as the acquired immunodeficiency syndrome (AIDS), in cancer therapy, and in sterilization of banked blood products.
传统光疗的一个主要缺点是，在光化学物质与靶恶性细胞、病毒感染细胞或病毒结合后，需要原位提供刺激光能量。这一缺点导致光化学物质在光医学中的应用受到很大限制。为了解决这个问题，我们研究了一种溴化1,8-萘二甲酰亚胺光化合物LY66Br [3-溴-4-(己基氨基)-N-己基-1,8-萘二甲酰亚胺]的抗病毒效果，该化合物在420nm可见光照射下可独立于氧气产生一种或多种稳定的抗病毒分子光产物（例如，被“预激活”）。感染1型人类免疫缺陷病毒（HIV-1）或1型人类嗜T淋巴细胞病毒（HTLV-I）的人类细胞系，在暴露于LY66Br的光化学产物（P-LY66Br）后，在体外完全丧失了形成合胞体的能力。P-LY66Br的光产物分别在室温及-80℃储存时，至少3周和6周内保持完全的抗病毒活性。有效抑制HIV-1和HTLV-I介导的合胞体形成的P-LY66Br浓度，对全血中的正常红细胞成分（红细胞2,3-二磷酸甘油酸、三磷酸腺苷、渗透脆性或血型抗原）无毒。此外，在静脉推注接种以达到600μM的P-LY66Br血浆浓度后，小鼠未表现出急性毒性迹象。这些发现首次证明了光化学产物可抑制逆转录病毒诱导的合胞体形成，并为进一步研究光化学物质在治疗系统性病毒感染（如获得性免疫缺陷综合征（AIDS））、癌症治疗及血库血液制品消毒中的预激活过程提供了依据。
