الفهرس | Only 14 pages are availabe for public view |
Abstract Hepatitis C virus (HCV) infection and its associated major complication, hepatocellular carcinoma (HCC) are challenging health concerns in Egypt and worldwide. As a result of the limited therapeutic effect, serious side effects and high cost of the currently available drugs, there is a real need for an alternative and more effective medication to overcome these serious diseases. Benzofurans and their bioisosteres, benzimidazoles and indoles were remarkably reported as anti-HCV and anticancer agents. A lot of compounds containing these heterocyclic systems were shown to act against HCV and cancer through various mechanisms. The present study targeted the design of novel hybrid derivatives having dual pharmacological activity as anti-HCV and anticancer agents. Various hybrid derivatives were synthesized to contain both an anti-HCV pharmacophore (benzofuran or benzimidazole) attached to thiazolidinone or rhodanine rings at different positions through linkers of various lengths) and anticancer pharmacophore (1,3-diaryl-1H-pyrazoles or substituted isatins). Moreover, the newly synthesized derivatives were biologically investigated for their anti-HCV and anticancer activities. In addition, a molecular modeling study was carried out to select derivatives with the best binding affinities to be synthesized, and also to explain the results of the biological investigation. The present thesis comprises the following chapters: Chapter I: Introduction This chapter shows in brief some basic information about HCV, its molecular virology and its relation to HCC. In addition, some previously reported benzofurans, benzimidazoles and indoles together with their biological activities as anti-HCV and anticancer agents are covered in this chapter, focusing on the recent reports. Chapter II: Research Objectives This chapter illustrates the aim of the present work and the rationale according to which the newly synthesized compounds were designed. Chapter III: Discussion This chapter discusses the theoretical bases of the methods adopted for the synthesis of the intermediates and final designed compounds with reference to the knowledge available in the literature. It includes three parts: Part 1: It describes the preparation of the first intermediates 1-[1-(benzofuran-2- yl)ethylideneamino]-3-substituted thioureas and 1-[1-(1H-benzimidazol-2-yl)ethylideneamino]- 3-substituted thioureas(2.1-2.9) through the reaction of 2-acetylbenzofuran or 2- acetylbenzimidazole with the appropriately substituted thiosemicarbazide. |