The Grapefruit Effect: Interaction between Cytochrome P450 and Coumarin Food Components, Bergamottin, Fraxidin and Osthole. X-ray Crystal Structure and DFT Studies.

Coumarins are plant-derived secondary metabolites. The crystal structure of three coumarins-bergamottin, osthole and fraxidin-are described and we analyze intermolecular interactions and their role in crystal formation. Bergamottin is a furanocoumarin found in citrus plants, which is a strong inhibitor of the principal human metabolizing enzyme, cytochrome P450 3A4 (CYP3A4). The crystal structure determinations of three coumarins give us the geometrical parameters and reveal the parallel-displaced π-π stacking and hydrogen bonding intermolecular interactions used for molecular assembly in the crystal structure. A quite strong (less than 3.4 Å) stacking interaction of bergamottin appears to be a determining feature that distinguishes it from other coumarins studied in this work. Our DFT computational studies on the three natural products of the same coumarin family docked into the active site of CYP3A4 (PDB 4D78) show different behavior for these coumarins at the active site. When the substrate is bergamottin, the importance of π-π stacking and hydrogen bonding, which can anchor the substrate in place, appears fundamental. In contrast, fraxidin and osthole show carbonyl coordination to iron. Our docking calculations show that the bergamottin tendency towards π-π stacking is important and likely influences its interactions with the heme group of CYP3A4.

Evaluation of virologic suppression rates during the COVID-19 pandemic with outpatient interdisciplinary HIV care.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has presented social distancing challenges leading healthcare systems to adapt and utilize telemedicine platforms more than ever before. Reducing patient exposure to COVID-19 became a primary concern, especially for populations at an increased risk for severe illness, such as human immunodeficiency virus (HIV) positive patients. Objectives: The primary objective of this study was to measure the impact of pharmacy services including telehealth through the percentage of virologically suppressed patients (HIV ribonucleic acid [RNA] < 200 copies/mL) during the pre-COVID and post-COVID time periods. Secondary objectives included the percentage of patients with undetectable viral loads (HIV RNA < 20 copies/mL), percentage of patients with cluster of differentiation 4 (CD4) cell counts greater than 200 cells/mm3, and changes in CD4 cell counts and percentages pre-COVID and post-COVID. Methods: This was a retrospective chart review at a single center HIV primary care clinic in Brooklyn, NY evaluating electronic medical records (EMRs) of 211 HIV-positive patients. Pre-COVID was defined as 1 year prior to March 13, 2020, and post-COVID was defined as March 13 to July 20, 2020. Results: Viral load suppression rates for pre and post-COVID were 88.6% and 85.3%, respectively (P = .28). Undetectable viral load rates for pre and post-COVID were approximately 81.5% and 74.4% (P = .096). Mean CD4 cell counts and percentages were 617 cells/mm3 and 29% for pre-COVID, and 460 cells/mm3 and 22% for post-COVID. CD4 cell counts greater than 200 cells/mm3 pre-COVID and post-COVID was 92.6% and 78.3%, respectively (P = .001). Conclusion: Utilization of pharmacy services including telehealth, may allow clinical pharmacists to collaboratively provide remote services without jeopardizing patient outcomes. Larger studies are needed to confirm these findings, and display the long-term impact and satisfaction of these services.

Emodin Scavenging of Superoxide Radical Includes π-π Interaction. X-Ray Crystal Structure, Hydrodynamic Voltammetry and Theoretical Studies.

The naturally occurring anthraquinone emodin is found in many plants that have been part of traditional Chinese medicine (TCM) for thousands of years. Recent pharmacological studies suggest that emodin might be a valuable therapeutic option for the treatment of various diseases. We describe the antioxidant effects of emodin on the superoxide radical. Our techniques include X-ray crystallography, density functional theory (DFT), and a recently developed cyclovoltammetry improvement, the rotating ring-disk electrode (RRDE) method. X-ray results show offset π-π stacking of emodin units in the crystal, and this type of interaction is supported by the DFT, which indicates one superoxide interacting via π-π stacking with the quinone moiety, by transferring one electron to the ring, and inducing some quinone aromatization. The second superoxide seems to form a stable complex after interacting with the H(hydroxyl) in position 3 of emodin. We show that one molecule of emodin sequesters two molecules of superoxide: one forming a complex with H(hydroxyl) in position 3, and the other due to π-π oxidation of superoxide and emodin ring reduction. We conclude that emodin is a very strong antioxidant. Color variation in the voltaic cell was observed during the RRDE study. This was analyzed and explained using a mini-grid gold electrode for UV-Vis spectroscopy in the voltaic cell.