Description
- Abstract:
- Infectious agents pose a significant threat to global health with profound health and economic implications. Particularly concerning is the emergence of epidemic-competent and life-threatening drug-resistant infectious agents. For example, the COVID19 pandemic has had a devastating effect on every facet of our lives (in less than 3years- 500 million infected, 6.2 million deaths and over 16 trillion dollars in cost). Moreover, persistent/drug resistant pathogens like Mycobacterium tuberculosis, Candida species and Plasmodium falciparum continue to have a devastating impact on global health. Historically, anti-infective drugs have revolutionized the practice of medicine and mounted an effective response to infectious agents. However, the evolution of resistant pathogens and emergence of epidemic-competent pathogens have left us playing catch-up. Evidently, we are in dire need of novel approaches to anti-infective drug discovery. This dissertation describes our unconventional strategies towards the discovery of anti-infectives to combat newly emerging pathogens as well as drug resistant pathogens. These efforts involve a three-pronged approach to combating infections agents. Broadly, these efforts deploy diversity-oriented synthesis to access and explore novel chemical scaffolds towards different anti-infective applications. The first is host modulation as a strategy to develop novel, broad-acting anti-infectives that combats newly emerging pathogens. Secondly, I describe the discovery/optimization of novel molecules that suppresses drug resistance in Candida species by restoring the activity of azole antifungals. Finally, I leveraged diversity-oriented synthesis to explore perturbation of fungal membrane physiology as a strategy to develop novel antifungals for several fungal pathogens including Candida, Cryptococcus and Saccharomyces species.
- Notes:
- Thesis (Ph. D.)--Brown University, 2022
Citation
Alabi, Philip Ephraim,
"Advancing Anti-infective Discovery via Diversity-Oriented Synthesis"
(2022).
Chemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:zkafdb2q/
