Medicine and Health Sciences Commons^™

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh

Theses & Dissertations

Over the past decade, work from our laboratory has demonstrated the potential of targeted nanoformulated antiretroviral therapy (nanoART) to produce sustained high plasma and tissue drug concentrations for weeks following a single intramuscular (IM) administration that can suppress ongoing viral replication and mitigate dose associated viral resistance. While progress has occurred towards developing long-acting nanoformulations for protease and nonnucleoside reverse transcriptase (RT) inhibitors, development of nanoformulations of hydrophilic nucleoside RT inhibitor drugs have remained elusive. Abacavir (ABC); a hydrophilic molecule exhibited limited utilities to develop into long-acting nanoformulation platform. Furthermore, inefficient conversion of ABC to its biological active metabolites; carbovir …

Design And Synthesis Of Novel Sultams As Non-Nucleoside Inhibitors Of Hiv Reverse Transcriptase, Brian Chadwick Lecroix

Doctoral Dissertations

The compound 2-methyl-3-phenyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (NSC 108406) was identified as an HIV-1 reverse transcriptase inhibitor by the National Cancer Institute. Using this lead, the Baker group has developed a series of analogues with various groups at the 3-position that show a spectrum of biological activities. In the end, the substituents used could not compare to the biological activity of the inhibitor efavirenz (Sustiva^® [trademark]), and so it was decided to synthesize sultams with alkylethynyl substituents at the 3-position of the sultams in an attempt to mimic the activity of efavirenz.

Previous research analyzed the proposed novel sultams in the modeling …

Comparison Of Methodologies For Synthesis Of 3-(Cyclopropylethynyl)Benzisothiazole 1,1-Dioxide, Rachel Lee Naramore

Chancellor’s Honors Program Projects

No abstract provided.

Is Tesamorelin A Safe And Effective Drug To Treat Lipodystrophy In Hiv Patients?, Jazmine A. Cole

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not Tesamorelin is a safe and effective drug to treat lipodystrophy in HIV patients.

Study Design: Review of three English language primary randomized controlled trials published between 2005-2010.

Data Sources: Randomized, placebo-controlled, double-blind clinical trials comparing Tesamorelin to a visually matched placebo were found using PubMed.

Outcome(s) Measured: Each of the three clinical trials assessed the improvement of lipodystrophy (accumulation of visceral adipose tissue) in HIV patients. In addition, they noted how the improvement in lipodystrophy would impact patient's self body image and quality of life. Prior …

Preventing Mother-To-Child Transmission Of Human Immunodeficiency Virus-1 (Hiv-1): Effects Of Intrapartum And Neonatal Single-Dose Nevirapine Prophylaxis And Subsequent Hiv-1 Drug Resistance At Antiretroviral Treatment Initiation, Amanda L. Harmon

CMC Senior Theses

The prevention of mother-to-child transmission is one of the most powerful tools in human immunodeficiency virus type 1 (HIV-1) prevention and has huge potential to improve both maternal and child health. In the absence of any preventative measures, infants born to and breastfed by their HIV-positive mothers have roughly a one-in-three chance of acquiring the infection themselves. HIV can be passed on from mother-to-child during pregnancy, during labor and delivery, and even after during breastfeeding.

Intrapartum and neonatal single-dose nevirapine (sd-NVP) is the foundation of preventing mother-to-child transmission in lower resource settings where it has been used alone or as …