Details

Autor(en) / Beteiligte

• Zangi, Maryam

Titel

Synthesis of Novel Antiparasitic Pyrazolopyrimidines and Antiviral N-Hydroxypyridones and N-Hydroxynaphthyridinones

Ort / Verlag

ProQuest Dissertations Publishing

Erscheinungsjahr

2023

Link zum Volltext

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• This dissertation encompasses three critical areas of research in the field of virology and parasitology: Herpes simplex virus (HSV), Cryptosporidium, and Hepatitis B virus (HBV). Each of these topics presents unique challenges and opportunities for advancing our understanding of viral and parasitic infections and developing novel therapeutic strategies.Herpes Simplex Virus (HSV):Herpes simplex viruses, particularly HSV-1 and HSV-2, are widespread among the human population, often residing dormant in sensory ganglia. They can reemerge under various triggers, causing symptoms or leading to viral transmission. While nucleoside analogs like acyclovir have been the standard of care, they face limitations in curbing viral replication, especially in cases of drug-resistant strains. Chapter two explores alternative treatments, with a particular focus on ciclopirox olamine and its derivatives, which have shown remarkable efficacy against both HSV-1 and HSV-2. These new potential lead compounds for optimization, offering hope for more effective herpesvirus control.Cryptosporidiosis:Cryptosporidium, a parasitic protozoa genus, is responsible for the waterborne diarrhea disease cryptosporidiosis globally, particularly affecting children in regions with limited access to clean water. Despite its significant impact on public health, there are no vaccines, and existing treatments are limited in efficacy. Nitazoxanide, the most widely used drug for cryptosporidiosis, has shortcomings such as adverse effects including headache, nausea, or stomach/abdominal pain,2especially in immunocompromised patients. Chapter three delves into the challenges posed by Cryptosporidium and discusses promising new drug classes, represented by pyrazolopyrimidine SLU-2815, that offer potential alternatives for treating this parasitic infection. The development of improved analogs is crucial for providing more effective therapeutic options.Hepatitis B Virus (HBV):Hepatitis B virus is a major public health concern, affecting millions of individuals worldwide, particularly in developing countries. HBV's resistance to environmental factors and its ability to transmit through various bodily fluids make it a formidable adversary. While hepatitis B vaccination effectively prevents new infections, treatment options for chronic cases remain limited, often focusing on controlling viral replication rather than achieving a complete cure. Chapter four focuses on exploration of the promising lead compound series of N-hydroxynaphthyridinones (HNOs) for HBV treatment. These compounds show significant potential for inhibiting HBV replication, offering hope for enhanced therapeutic strategies. The research explores the optimization of HNO analogs and the synthesis of new lead compounds, aiming to improve their antiviral efficacy.This dissertation aims to contribute to the advancement of our understanding of these viral and parasitic infections and the development of more effective treatments. By exploring alternative therapeutic strategies, optimizing existing lead compounds, and expanding our knowledge of the structural-activity relationships, we strive to address the significant public health challenges posed by HSV, Cryptosporidium, and HBV.