The synthesis and structure-activity relationships of biologically active anthraquinones

It was reported in 1982 (Raimondi, L., et.al. Pharmacol. Res. Commun. 1982, 14, 103) that rhein, a naturally occurring anthraquinone, and several of its synthetic analogues, inhibit several proteases such as carboxypeptidase A, trypsin, pepsin and elastase. Based upon this report a large series of anthraquinone analogues related to rhein were prepared and assayed for their ability to inhibit human leukocyte elastase (HLE), a serine proteinase which has been implicated in pathological states characterized by abnormal degradation of connective tissue, such as pulmonary emphysema and rheumatoid arthritis. In addition, it was found that some of the inhibitors prepared also inhibit cathepsin G (CatG), a closely related serine proteinase.;The structure-activity relationships derived from this study found that analogues consisting of the 2-alkyl-1,8-dihydroxyanthraquinone substructure inhibit HLE with IC;Additionally, a series of variously substituted anthraquinones were assayed in an in vitro screen for activity against human immunodeficiency virus (HIV), the causative entity of acquired immunodeficiency syndrome (AIDS). These experiments were conducted following a report that hypericin, a naturally occurring extended quinone, effectively inhibited several retroviruses in vitro and in vivo (Meruelo, D., et.al. Proc. Natl. Acad. Sci. USA 1988, 85, 5230). The results of the experiments concluded that simple anthraquinone analogues possess no significant antiretroviral activity. A series of compounds structurally related to hypericin, possessing the bianthrone ring nucleus, was prepared and submitted for anti-HIV assay. Unfortunately, the results of these assays were unavailable at the time of this writing.