Title

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.

Faculty Mentor(s)

Levente Fabry-Asztalos

Department/Program

Chemistry

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May 15th, 3:30 PM May 15th, 5:00 PM

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