Medicinal and Pharmaceutical Chemistry Commons^™

Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).

Methods

Eight-month-old female 3xTg-AD mice were injected intraperitoneally with …

A Novel Micropeptide, Slitharin, Exerts Cardioprotective Effects In Myocardial Infarction, Ahmed G. E. Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán

Pharmacy Faculty Articles and Research

Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type.

Experimental design: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction.

Results: We identified a novel 24-amino acid micropeptide …

Six-Month Report Assessing The Feasibility And Effectiveness Of Amniotic Membrane Injections In Patients With Short, Anterior, Urethral Strictures, Nicholas Pryde, Jack Vernocke, Aron Liaw, Michael Sessine, Nivedita Dhar

Medical Student Research Symposium

Introduction: Urethral stricture treatment has high recurrence rates and adjunct injectable agents have been explored. Amniotic membranes (AM) promote apoptosis of pro-inflammatory cells, prevent differentiation of pro-fibrotic cells, and decrease scar formation. These tissues generated interest in reconstructive urethral surgery. Thus, we performed urethral dilation combined with micronized AM injection in urethral scar tissue for treatment of urethral stricture.

Materials and Methods: Adult males with strictures ≤12Fr in diameter and ≤2 cm in length, International Prostate Symptom Score (IPSS) ≥11 and maximum flowrate <15 ml/s. Reconstituted 100mg micronized AM was injected at the time of urethral dilation. Primary study end point was anatomical success (≥14Fr by cystoscopy) at 6 months. Secondary end points were questionnaires, flow rate, and post void residual. Outcomes assessed at baseline, 5 days, 14 days, 3 months, and 6 months post-injection. Safety was analyzed.

Results: Ten men, mean age of 52 ± 15 years, were included. There were 7 patients with …

Repurposing Of Us-Fda-Approved Drugs As Negative Modulators Of Ubiquitin Specific Protease-7 (Usp7), Seema Zadi, Sumaira Javaid, Atia-Tul-Wahab, Humaira Zafar, Muhammad Awais, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of …

Genome-Wide Mutagenesis To Investigate The N-Terminal Methylome: The Protective Effects Of Hsp31 And Other Methylated Proteins In Yeast, James Rooney, Jacob Lindsey

The Journal of Purdue Undergraduate Research

The purpose of this study was to understand the role of methylation in regulating the cellular stress response of Hsp31 in Saccharomyces cerevisiae yeast cells. Hsp31 is known to be methylated by the N-terminal methyltransferase Tae1. Changing the methylation site can affect the methylation status of Hsp31, which may play a role in the protective activity of Hsp31 against cellular stress. GLO1 is a gene in yeast involved in catalyzing the detoxification of methylglyoxal (MGO), which is a by-product of glycolysis. We established that S. cerevisiae in the glo1Δ and background is sensitive to cellular stress by MGO. Mutant strains …

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, Dony Ang, Cyril Rakovski, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards …

Behavioral Effects Of Novel Treatments For Pain Using Different Pathways, Danya M I Aldaghma

Theses and Dissertations

Pain is defined as an unpleasant sensation that is mostly caused by a stimulus from our surroundings. This sensation has the potential to become a significant concern, disrupting daily activities, and diminishing overall quality of life. However, it could also hold significant importance as it serves as a protective mechanism. Pain acts as an alarm system for the human body, alerting it to potentially harmful situations where tissues may be at risk of damage1. Despite the considerable advancements in pain treatment and the extensive knowledge scientists possess regarding the pathophysiology and pathways of pain, numerous medications aimed at alleviating pain …

Increasing The Efficacy Of Actinomycin D With Resveratrol In Aerodigestive Tract Cancers, Lukmon Morenikeji Raji

Theses, Dissertations and Capstones

Chemotherapy poses a significant challenge for cancer patients due to drug-associated toxicity, which often results from their effects on both healthy (normal) and cancerous cells. While various options aim to reduce toxicity and optimize beneficial effects, a comprehensive solution remains elusive. Cyclotherapy is one such approach developed to protect normal cells from the toxic effects of chemotherapy drugs. The basic principle underlying cyclotherapy is p53- dependent cell cycle arrest of normal cells while killing cancer cells via a p53-independent mechanism using a second drug. In our research, we investigated the inhibitory effects of a combination of two low-dose anticancer drugs, …

Investigating The Association Of Demographic Factors On Methotrexate Delay-Clearance And Toxicity In Pediatric Oncology Patients: A Retrospective Chart Review, Belal Alabdul Razzak

Honors Undergraduate Theses

High-dose methotrexate (HD MTX) is critical for treating pediatric malignancies such as acute lymphoblastic leukemia and neuro-carcinoma. However, its significant toxicity due to drug accumulation poses substantial risks. This retrospective study assesses the impact of demographic factors on MTX toxicity and clearance in pediatric oncology patients. Patient records from Saint Mary Hospital were analyzed, focusing on two MTX administration protocols: a 24-hour infusion followed by alkaline hydration and a 4-hour infusion followed by alkaline hydration. We hypothesize that factors such as age, body surface area (BSA), and body mass index (BMI) are associated with MTX clearance and toxicity. The study …

Design, Synthesis, Molecular Docking, And Molecular Dynamic Studies Of Novel Quinazoline Derivatives As Phosphodiesterase 7 Inhibitors, Marwa M. Safar Prof. Dr.

Pharmacy

Introduction: Phosphodiesterase 7 (PDE7) is a high-affinity cyclic AMP (cAMP)- specific PDE that is expressed in immune and proinflammatory cells. In this work, we explore the possibility that selective small molecule inhibitors of this enzyme family could provide a novel approach to alleviate the inflammation that is associated with many inflammatory diseases. Methods: A series of novel substituted 4-hydrazinoquinazoline derivatives and fused triazoloquinazolines were designed, synthesized, and evaluated in vitro for their PDE7A inhibition activities, in comparison with Theophylline, a non-selective PDE inhibitor, and BRL50481, a selective PDE7A inhibitor. This series of novel quinazoline derivatives were synthesized via multi-step reactions. …

Clinical Practice Guideline For The Management Of Depression In Primary Care, Estrella Catherine Villarreal

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Background: The prevalence of depression poses a significant challenge in primary care, emphasizing the urgent need to address this issue during patient visits. Primary care providers are at the forefront of managing depression, yet they encounter difficulties in screening, diagnosing, assessing, and treating this complex condition. Clinical guidelines serve as valuable tools for primary care providers and practices, offering support in identifying and addressing depression effectively. An evidence-based approach to treating depression in primary care, with a focus on collaborative interventions with behavioral health to enhance depression management for American Indian/Alaskan Native (AI/AN) communities.

Methods: The descriptive analysis was conducted …

In Silico Identifcation Of New Potential Inhibitors Of Quorum Sensing By Gram‑Positive Bacteria Through Specialized Molecular Docking, Amgad Albohy, Najla A. Obaid, Mariam Mojally, Mohammed Abou Rehab, Najd Ahmad Alkhudhir

Pharmacy

Quorum sensing is the process by which bacterial cells can communicate by producing substances to regulate viable processes such as gene expression, virulence, and bioflm formation. Gram-positive bacteria such as Staphylococcus aureus and Enterococcus faecalis have specifc enzymes (autoinducers) that control the quorum sensing system. Sortase A is a surface protein that regulates virulence and cell‒cell communication in Gram-positive bacteria. To interfere with this system and reduce virulence and cell‒cell communication, quorum sensing inhibitors are used, which are nonantibiotic substances. In this study, we aimed to use Food and Drug Administration-approved drugs (analgesics and antipsychotics) and investigate their activity using …

Exploration Of Dopaminergic And Serotonergic Pathways Utilizing Pleiotropic Agents, Charles B. Jones Iii

Theses and Dissertations

2-(Benzoyl)piperidines (BPs) are at a crossroads of therapy and abuse. These compounds are a hybrid between the ADHD medication methylphenidate and abused stimulant cathinones. Here we use computational molecular modeling, synthesis, mutagenesis, and epifluorescence microscopy to further improve the understanding of and potential treatments for several neuropsychiatric disorders. Utilizing the BP scaffold and controlling chirality and aryl substitution, these agents were examined at DAT and SERT. From these investigations it has now been established that R isomer BPs are favored for DAT while S isomer BPs are favored for SERT. Aryl-substitution can greatly affect the selectivity of these agents with …

Ai Renaissance: Pharmaceuticals And Diagnostic Medicine, Ty J. Feeney, Michael S. Sinha

All Faculty Scholarship

The explosive growth of Artificial Intelligence (AI) in the modern era has led to significant advancements in the world of medicine. In drug discovery, AI technology is used to classify proteins as drug targets or non-targets for specific diseases, more accurately interpret and describe pharmacology in a quantitative fashion, and predict protein structures based on only a protein sequence for input. AI methods are used in drug development to generate predictive models for drug screening purposes, refine and modify candidate structures of drugs to optimize compounds, and predict a drug’s physiochemical properties, bioactivity, and toxicity. For medical devices, the advancement …

Dual Activity Of Aromatic And Heterocyclic Compounds As Anti-Inflammatory And Anticancer Promising Agents, Samar Said Fatahala, Rania Helmy Abd El-Hameed, Mosaad Sayed Mohamed, Neama Abdallah Abd El-Tawab

Trends in advanced sciences and technology

As the second leading cause of mortality worldwide, cancer poses a severe threat to human health. Chronic inflammation has recently been linked to an increased risk for a number of malignancies, suggesting that reducing inflammation could be a useful approach to both cancer prevention and treatment. This review delves into the connection between inflammation and cancer and outlines the current use of anti-inflammatory drugs as potentially effective cancer prevention and therapy strategies. we herein describe the main relation and the mechanisms underlying the anti-cancer outcomes of anti-inflammatory agents; namely Non-Steroidal Anti-inflammatory Drugs (NSAIDs), COX-2 inhibitors, LOX-inhibitors, Toll- inhibitors, and antioxidant …

Molecular Docking Analysis Of Acanthus Ilicifolius Compounds Toward Cul4b-Ddb1-Ahr-Erα Complex Protein For Antiosteoporosis Discovery, Binar Asrining Dhiani, Sarmoko Sarmoko, Retno Wahyuningrum, Akbar Yulianto

Pharmaceutical Sciences and Research

Osteoporosis represents a significant global public health issue, particularly among the aging population. Its incidence reaches 18.3% of the total population, with the highest prevalence observed in elderly postmenopausal women. A key factor in osteoporosis is the decreased expression level of estrogen receptor alpha (ERα), attributed to its degradation by the ubiquitin ligase protein complex Cullin4B (CUL4B), DNA damage binding 1 (DDB1), and aryl hydrocarbon receptor (AhR), collectively known as CUL4BAhR. Acanthus ilicifolius L contains compounds exhibiting antiosteoporosis activity, primarily by inhibiting osteoclastogenesis via RANKL. However, no reports exist of antiosteoporosis agents that act by inhibiting ERα degradation via CUL4BAhR. …

The Concise Guide To Pharmacology 2023/24: Enzymes, Stephen P. H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, James A. Davies, Stephanie Annett, Detlan Boison, Kathryn Elisa Burns, Carmen Dessauer, Jürg Gertsch, Nuala Ann Helsby, Angela A. Izzo, Rennolds Ostrom, Andreas Papapetropoulos, Nigel J. Pyne, Susan Pyne, Tracy Robson, Roland Seifert, Johannes-Peter Stasch, Csaba Szabo, Mario Van Der Stelt, Albert Van Der Vliet, Val Watts, Szu Shen Wong

Pharmacy Faculty Articles and Research

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the …

Structural Analysis And Activity Correlation Of Amphiphilic Cyclic Antimicrobial Peptides Derived From The [W4R4] Scaffold, Shaima Ahmed El-Mowafi, Anastasia G. Konshina, Eman H. M. Mohammed, Nikolay A. Krylov, Roman G. Efremov, Keykavous Parang

Pharmacy Faculty Articles and Research

In our ongoing quest to design effective antimicrobial peptides (AMPs), this study aimed to elucidate the mechanisms governing cyclic amphiphilic AMPs and their interactions with membranes. The objective was to discern the nature of these interactions and understand how peptide sequence and structure influence antimicrobial activity. We introduced modifications into the established cyclic AMP peptide, [W₄R₄], incorporating an extra aromatic hydrophobic residue (W), a positively charged residue (R), or the unique 2,5-diketopiperazine (DKP). This study systematically explored the structure–activity relationships (SARs) of a series of cyclic peptides derived from the [W₄R₄] scaffold, …

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

A Gold-Based Inhibitor Of Oxidative Phosphorylation Is Effective Against Triple Negative Breast Cancer, R. Tyler Mertens, Jong Hyun Kim, Samuel Ofori, Chibuzor Ngozi Olelewe, Paul J. Kamitsuka, Gunnar F. Kwakye, Samuel G. Awuah

Markey Cancer Center Faculty Publications

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mito- chondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its thera- peutic potential following systemic …

Ozgene: To Advance Humanity – Inspire Curiosity, Maarit Patrick, Mike Dixon

Huntsman School of Business Teaching Scholarship Series

The case introduces the students to Ozgene, an Australian firm that experienced a dramatic reduction in lead time of their products because of implementation of Lean principles. The case can be used in undergraduate or graduate courses in operations management or supply chain management as an introduction to Lean principles. The case also encourages students to consider the challenges that make-to-order differ from those of make-to-stock and explore production design principles.

Tolfenamic Acid Derivatives: A New Class Of Transcriptional Modulators With Potential Therapeutic Applications For Alzheimer’S Disease And Related Disorders, Juanetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ourarhni, Nasser H. Zawia

Pharmacy Faculty Articles and Research

The field of Alzheimer’s disease (AD) has witnessed recent breakthroughs in the development of disease-modifying biologics and diagnostic markers. While immunotherapeutic interventions have provided much-awaited solutions, nucleic acid-based tools represent other avenues of intervention; however, these approaches are costly and invasive, and they have serious side effects. Previously, we have shown in AD animal models that tolfenamic acid (TA) can lower the expression of AD-related genes and their products and subsequently reduce pathological burden and improve cognition. Using TA as a scaffold and the zinc finger domain of SP1 as a pharmacophore, we developed safer and more potent brain-penetrating analogs …

Piperine Encourages Apoptosis In Human Cervical Adenocarcinoma Cells Through Ros Generation, Dna Fragmentation, Caspase-3 Activation And Cell Cycle Arrest, Asif Jafri, Juhi Rais, Sudhir Kumar, Md Arshad

Research Symposium

Background: Cancer is one of the most common destructive diseases and the second leading cause of death in humans. Among cancer, cervical cancer is the second most common malignancy among women globally. Thus, there is a continuous need to search for chemotherapeutic chemicals or naturally occurring drugs to resolve this global health problem. Piperine (1-piperoylpeperdine) is present in the fruits of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). It possesses several pharmacological properties and in the present study we have evaluated its anti-cancer potential on human cervical adenocarcinoma (HeLa) cells.

Methods: The anti-proliferative effect …

Oral Dosages Of The Nsaid Aspirin Decreased The Growth Rate Of Species Found In The Human Gut Microbiome Including Akkermansia Muciniphila, Bacteroides Fragilis, Clostridium Sordellii, And Clostridium Difficile, Wyatt H. Greenbaum, Garrett J. Greenbaum, Anna Spiezio

PANDION: The Osprey Journal of Research and Ideas

Over past few decades, new insight has been revealed in the scientific community about the importance of the human gut microbiome relating to general health. It is known that imbalances in the species that reside in the human gut can cause organism-wide problems in humans. When prescribing or injecting oral medications, the thought of the downstream effects on the gut microbiome are not always considered. By exposing known healthy members of the gut; Akkermansia muciniphila, Bacteroides fragilis, Clostridium sordellii, and Clostridium difficile to the Aspirin, this study attempted to provide insight into the effects of the drug on bacterial growth. …

Design, Molecular Modelling And Synthesis Of Novel Benzothiazole Derivatives As Bcl-2 Inhibitors, Amira Khalil, Hoda S. Ismail, Dalal A. Abou El Ella, Deena S. Lasheen, Rabah A. Taha

Pharmacy

Apoptosis plays a crucial role in cancer pathogenesis and drug resistance. BCL-2 family of enzymes is considered as one of the key enzymes which is involved in apoptosis. When there is disruption in the balance between anti-apoptotic and pro-apoptotic members of the BCL-2 family apoptosis is dysregulated in the affected cells. Herein, 33 novel benzothiazole-based molecules 7a-i, 8a-f, 9a-b, 12a-e, 13a-d, 14a,b, and 17a-j were designed, synthesized and tested for their BCL-2 inhibitory activity. Scaffold hopping strategy was applied in designing of the target compounds. Compounds 13c and 13d showed the highest activity with IC50 values equal to 0.471 and …

Structural Features Of Thyroglobulin Linked To Protein Trafficking, Cintia E. Citterio, Kookjoo Kim, Bhavana Rajesh, Kevin Pena, Oliver Biggs Clark, Peter Arvan

Pharmacy Faculty Articles and Research

Thyroglobulin must pass endoplasmic reticulum (ER) quality control to become secreted for thyroid hormone synthesis. Defective thyroglobulin, blocked in trafficking, can cause hypothyroidism. Thyroglobulin is a large protein (~2750 residues) spanning regions I–II–III plus a C-terminal cholinesterase-like domain. The cholinesterase-like domain functions as an intramolecular chaperone for regions I–II–III, but the folding pathway leading to successful thyroglobulin trafficking remains largely unknown. Here, informed by the recent three-dimensional structure of thyroglobulin as determined by cryo-electron microscopy, we have bioengineered three novel classes of mutants yielding three entirely distinct quality control phenotypes. Specifically, upon expressing recombinant thyroglobulin, we find that first, mutations …

Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal

The Undergraduate Research Journal

Diadema savignyi spine extract in an experimental setup using L929 cell line in vitro. The cell metabolic activity of L929 cells is tested through an MTT assay. The sea urchin spine extract is applied to the cells in two concentrations: 100 μg/ml (136% viability) and 200 μg/ml (95% viability). The bioactive components of the sea urchin spine are identified via GC-MS, and the antioxidant and anti-inflammatory activities are evaluated using catalase assay (CAT), glutathione (GSH), and nitric oxide (NO) tests. Results show that the GC-MS identified bioactive components including the anti-inflammatory and anti-irritant bisabolol oxide and the pro-inflammatory oleic acid. …

Probing The Activation Mechanisms Of Agonist Dpi-287 To Delta-Opioid Receptor And Novel Agonists Using Ensemble-Based Virtual Screening With Molecular Dynamics Simulations., Emily Dean, Annemarie Dominique, Americus Palillero, Annie Tran, Nicholas Paradis, Chun Wu

College of Science & Mathematics Departmental Research

Pain drugs targeting mu-opioid receptors face major addiction problems that have caused an epidemic. The delta-opioid receptor (DOR) has shown to not cause addictive effects when bound to an agonist. While the active conformation of the DOR in complex with agonist DPI-287 has been recently solved, there are still no FDA-approved agonists targeting it, providing the opportunity for structure-based virtual screening. In this study, the conformational plasticity of the DOR was probed using molecular dynamics (MD) simulations, identifying two representative conformations from clustering analysis. The two MD conformations as well as the crystal conformation of DOR were used to screen …

Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa

Pharmacy

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and …