Steroid conjugates for applications in pharmacology and biology

Abstract

The scope of present study is rather broad and may seem to be non-uniform, covering subjects such as the treatment of insect pest species and atherosclerosis. Nevertheless, the magic word "steroid" connects the presented projects together. Steroid compounds possessing various unique physico-chemical and biological properties have been utilized as carriers of biologically active compounds. In this work novel conjugates of steroids with insecticidal agents (I. part), and anti-atherosclerotic drug (II. part) are presented. The first introductory part deals with the history, development and importance of novel insecticides. In the second part the metabolism of cholesterol, development of atherosclerosis and its treatment are discussed. The importance of polymorphism in drug discovery is stated in the end. Juvenoids, juvenile hormone analogues, environmentally safe insecticides, non-persistent, non-toxic for warm-blooded animals and fish, can become advanced compounds in regulating many aspects in insect physiology. Structure modification of juvenoids via juvenogen derivatives (hormonogenic substances) plays an important role in controlling the juvenoid liberation rate in the insect digestive system and can also play an important role in the mode of action toward different arthropod groups, with the focus on insect pest species. For that reason, racemic mixtures of juvenoid were esterified with hexadecanoic, butanoic, 3-methylbut-2-enoic and 3a,7a,12a-triformyloxy-5p-cholan-24-oic acid. Cholic acid-based juvenogens were further subjected to dimerization resulting in agents possessing two molecules of juvenoid in their structure, which was expected to lead to higher biological activity. A total of 20 new compounds with potential insecticidal activity were synthesized, characterized, and tested for their inhibitory activity on the reproduction of blowflies Neobellieria (Sarcophaga) bullata. Succinobucol, a hypolipidemic drug that possesses significant antioxidant and anti-inflammatory properties, was studied for its polymorphism with the result of four discovered polymorphs. With an idea to alter its pharmacological profile and carry the drug more efficiently through intestinal membranes its conjugates with plant stanol and sterols, as well as with cholesterol, were prepared, described and studied for their toxicity, antioxidant activity and availability.