Miskovsky Pavol
Department of Biophysics, P. J. Safarik University, Kosice, Slovak Republic.
Curr Drug Targets. 2002 Feb;3(1):55-84. doi: 10.2174/1389450023348091.
Hypericin, a naturally occurring pigment, is found in certain species of plants from the genus Hypericum, the most common of which is Saint John's Wort (Hypericum perforatum). Recent interest in hypericin is provoked by the discovery that it possesses extremely high toxicity towards certain viruses notably the class of enveloped viruses that includes human immunodeficiency virus (HIV) and toward tumors, and that this toxicity absolutely requires light. Consequently, a detailed understanding of the interaction of hypericin with cellular components (membranes, proteins, nucleic acids) and with light is of fundamental biological importance. The antiviral and antineoplastic activities of hypericin and its derivatives and its mode of action have been widely studied, in the last two decades. This review is focused on the results obtained in the study of hypericin heteroassociations with biological macromolecules, DNA and human serum albumin in particular. An alternative type of the hypericin photosensitizing activity associated with its ability to produce a photogenerated pH drop is discussed that and discussed in connection with its potential application in photodynamic therapy. In the review, it is also presented how an interdisciplinary approach supported by sophisticated techniques of optical spectroscopy and molecular modeling can be effectively applied for the identification of the specific binding sites of the drug in some biomacromolecules as well as for the determination of the physico-chemical mechanism'of the biological activity of hypericin.
金丝桃素是一种天然存在的色素,存在于金丝桃属的某些植物物种中,其中最常见的是圣约翰草(贯叶连翘)。最近对金丝桃素的兴趣源于发现它对某些病毒,尤其是包括人类免疫缺陷病毒(HIV)在内的包膜病毒类,以及对肿瘤具有极高的毒性,而且这种毒性绝对需要光。因此,详细了解金丝桃素与细胞成分(膜、蛋白质、核酸)以及与光的相互作用具有重要的生物学意义。在过去二十年中,金丝桃素及其衍生物的抗病毒和抗肿瘤活性及其作用方式得到了广泛研究。本综述重点关注在金丝桃素与生物大分子,特别是DNA和人血清白蛋白的异质缔合研究中获得的结果。讨论了与金丝桃素产生光致pH下降能力相关的另一种类型的光敏活性,并结合其在光动力疗法中的潜在应用进行了讨论。在综述中,还介绍了如何将由先进的光谱学技术和分子建模支持的跨学科方法有效地应用于确定药物在某些生物大分子中的特定结合位点,以及确定金丝桃素生物活性的物理化学机制。