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Antibiotic Drug Discovery Targeting Bacterial Metabolism, Miranda J. Wallace Aug 2019

Antibiotic Drug Discovery Targeting Bacterial Metabolism, Miranda J. Wallace

Theses and Dissertations (ETD)

Over the last century, the use of antibiotics has enabled many advances in modern medicine, making life as we know it possible. In recent years, however, emerging bacterial resistance to virtually all major antibiotic classes has resulted in a worldwide increase in morbidity, mortality, and financial burden associated with drug resistant infections. The antimicrobial resistance crisis presents an urgent need for new antimicrobials with distinct mechanisms of action from existing drugs. The current pharmaceutical pipeline of new antibiotics is limited due to three obstacles: a lack of understanding of resistance mechanisms, a dearth of novel mechanisms of action among new …


Investigating The Effect Of Rutaecarpine On The Benzo[A]Pyrene-Induced Dna Damage In Vitro, You Li Jan 2019

Investigating The Effect Of Rutaecarpine On The Benzo[A]Pyrene-Induced Dna Damage In Vitro, You Li

University of the Pacific Theses and Dissertations

Benzo[a]pyrene (BaP), is one of the most potent mutagens and carcinogens known. It requires metabolic activation through cytochrome P450 (CYP)1A1 to yield the ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE can bind to DNA and form predominantly covalent (+) trans adducts at the N2 position of guanine causing DNA damage. Rutaecarpine (RTC) is an herbal medicine that has been used to treat several diseases such as headache, hypertension, gastrointestinal disorders, amenorrhea, and anti-inflammation. It has also been reported as a potent inducer of CYP enzymes, including CYP1A1, and CYP1A2. The mechanisms underlying up-regulation of CYP1A1 by RTC is dependent on aryl …