Towards the Synthesis of Novel 1,3-Azaborines as Potential HIV-1 Protease Inhibitors
Document Type
Oral Presentation
Campus where you would like to present
Ellensburg
Event Website
https://digitalcommons.cwu.edu/source
Start Date
15-5-2019
End Date
15-5-2019
Abstract
Drug discovery for Human Immunodeficiency Virus (HIV) has resulted in life-saving therapies, making a large impact on modern medicine. However, current treatments are being met with high resistance rates towards HIV due to constant viral mutations, poor bioavailability, and patient noncompliance due to side effects. Consequently, there is an imperative need for the development of new lead compounds with lower toxicity, increased bioavailability, and higher binding affinity. Recent studies have shown boronmodified inhibitors have a higher inhibitory affinity for HIV-1 protease than the corresponding non-boron analogs. The main goal is to synthesize a library of cyclic and straight-chain boronates that may function as dual-mode, both associative and competitive, inhibitors of the HIV-1 protease. Cyclic boronates are expected to be more successful inhibitors due to their structural rigidity. However, some of the straight-chain boronates will mimic both sides of the scissile bond of the natural substrate; therefore, potentially resulting in higher binding affinities. The target boronates have the potential for greater affinity towards the protease enzyme, increased bioavailability, and fewer adverse side effects. In addition, the cyclic and straight-chain boronates being synthesized will serve to expand molecular diversity, as well as organoboron chemistry in general.
Recommended Citation
Dawson, Sean; Suarez, Cheyenne; and Vulcano, Audrey, "Towards the Synthesis of Novel 1,3-Azaborines as Potential HIV-1 Protease Inhibitors" (2019). Symposium Of University Research and Creative Expression (SOURCE). 81.
https://digitalcommons.cwu.edu/source/2019/Oralpres/81
Department/Program
Chemistry
Towards the Synthesis of Novel 1,3-Azaborines as Potential HIV-1 Protease Inhibitors
Ellensburg
Drug discovery for Human Immunodeficiency Virus (HIV) has resulted in life-saving therapies, making a large impact on modern medicine. However, current treatments are being met with high resistance rates towards HIV due to constant viral mutations, poor bioavailability, and patient noncompliance due to side effects. Consequently, there is an imperative need for the development of new lead compounds with lower toxicity, increased bioavailability, and higher binding affinity. Recent studies have shown boronmodified inhibitors have a higher inhibitory affinity for HIV-1 protease than the corresponding non-boron analogs. The main goal is to synthesize a library of cyclic and straight-chain boronates that may function as dual-mode, both associative and competitive, inhibitors of the HIV-1 protease. Cyclic boronates are expected to be more successful inhibitors due to their structural rigidity. However, some of the straight-chain boronates will mimic both sides of the scissile bond of the natural substrate; therefore, potentially resulting in higher binding affinities. The target boronates have the potential for greater affinity towards the protease enzyme, increased bioavailability, and fewer adverse side effects. In addition, the cyclic and straight-chain boronates being synthesized will serve to expand molecular diversity, as well as organoboron chemistry in general.
https://digitalcommons.cwu.edu/source/2019/Oralpres/81
Faculty Mentor(s)
Levente Fabry-Asztalos