Medicinal Chemistry and Drug Metabolism
Xenobiotic metabolism and probe design
1. We are investigating the stability, metabolism and reactivity of lignans and diphenylethanes. We have observed that di-catechol lignans can undergo intramolecular cyclizations under oxidizing conditions to form dibenzocyclooctadienes. We are continuing to prepare lignan and diphenylethane analogues in an effort to better understand the influence that substituents have on stability.
2. We have prepared a number of novel bifunctional compounds designed to interact with alpha-synuclein, a protein involved in the pathophysiology of Parkinson's Disease. We continue to design and prepare additional bifunctional compounds to probe binding to alpha-synuclein and improve binding properties.
3. We are designing synthetic pathways to prepare 18F-labelled compounds as Positron Emission Tomography imaging probes for both the lignans and bifunctional compounds.
Selected Research Publications
Chukwunonso K. Nwabufo, Omozojie P. Aigbogun, Kevin J.H. Allen, Madeline N. Owens, Jeremy S. Lee, Christopher P. Phenix and Ed S. Krol, 2021. Employing in vitro Metabolism to Guide Design of F-Labelled PET Probes of Novel alpha-Synuclein Binding Bifunctional Compounds. Xenobiotica, 50 (8), 885-900. doi.org/10.1080/00498254.2021.1943566
Wei Jin, Randy Purves, Ed Krol, Ildiko Badea, Anas El-Aneed, 2020. Mass Spectrometric Detection and Characterization of Metabolites of Gemini Surfactants Used as Gene Delivery Vectors. Journal of the American Society of Mass Spectrometry, 31 (2), 366-378. doi: 10.1021/jasms.9b00004
Ellen K. Wasan, Jinying Rita Zhao, Munawar Ali Mohammed, Jaweria Syeda, Jacqueline Cawthray, Joshua Poteet, Tatiana Orlowski, Chi Zhang, Brian M. Fahlman, Amanda Bunyamin, Kevin Soulsbury, Ed S. Krol, 2019. Development of a UV-Stabilized Topical Formulation of NIfedipine for the Treatment of Raynaud Phenomenom and Chilblains. Pharmaceutics, 11 (11), doi: 10.3390/pharmaceutics11110594
Chukwunonso K. Nwabufo, Anas El-Aneed, Ed S. Krol, 2019. Tandem Mass Spectrometric Analysis of Novel Caffeine Scaffold-Based Bifunctional Compounds for Parkinson’s disease, Rapid Communications in Mass Spectrometry, 33 (23), 1792-1803. doi: 10.1002/rcm.8540
Malcolm J. Daniels, J. Brucker Nourse, Hanna Kim, Valerio Sainati, Marco Schiavina, Maria Grazia Murrali, Buyan Pan, John J. Ferrie, Conor M. Haney, Rani Moons, Neal S. Gould, Antonio Natalello, Rita Grandori, Frank Sobbot, E. James Petersson, Elizabeth Rhoades, Roberta Pierattelli, Isabella Felli, Vladimir N. Uversky, Kim A. Caldwell, Guy A. Caldwell, Ed S. Krol, Harry Ischiropoulos, 2019, Cyclized NDGA modifies dynamic alpha-synuclein monomers preventing aggregation and toxicity, Scientific Reports, doi: 10.1038/s41598-39480-z
Ed S. Krol, Roy Thomas Dobson and Kunmi Adesina, 2019, The Association between Academic Success in a Professional Pharmacy Program and Performance in BSP and Pharm D Prerequisites at the University of Saskatchewan. American Journal of Pharmaceutical Education, 83 (1) Article 6491.
Isaac Asiamah, Ed S. Krol, 2018, Quadrupole Linear ion-trap Mass Spectrometry Studies on Glutathione Conjugates of Nordihydroguaiaretic acid (NDGA) Analogues Reveals Phenol-type Analogues are Without Reactive Metabolite-mediated Toxic Liability, Cogent Chem., doi: 10.1080/23312009.2018.1562858.