Medicinal and Pharmaceutical Chemistry Commons^™

Basic Structure Of The Pharmacophore Virtual Screening Protein 7kg7 For Candidate Therapeutic Options Covid-19, Ahmad Ridha Al Fiqri

Indonesian Journal of Medical Chemistry and Bioinformatics

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome, namely coronaviruses (SARS-CoV-2) has been a pandemic to date and is contagious with relatively high mortality rates. Various efforts have been made to control the pandemic to finding the best solution to reduce the spread such as rapid detection based on molecular and serological, as well as efforts to find the best medicine for COVID-19 patients continue to be carried out. We analyzed and concluded that the presatovir compound is capable of being a substitute for the native protein ligand 7KG7, this is proved with a ΔG value of -13.22 kcal/mol …

An Integrative Review Of The Absorption Of Fda-Approved Chemical Sunscreen Filters Into The Blood, Srinidhi Banala, Samrat Gollapudi, Abhiram Gollapudi, Bhaumik Patel

Rowan-Virtua Research Day

Introduction: This integrative review examines the absorption of FDA-approved chemical sunscreen filters, specifically avobenzone and oxybenzone, into the bloodstream. The study aims to compare the levels of absorption and potential health effects of systemic exposure to these sunscreen ingredients in the United States.

Methods: The researchers conducted a literature search of 57 articles, of which 15 were used for the review. Inclusion criteria focused on studies discussing absorption levels of avobenzone and oxybenzone, as well as methods of absorption into the bloodstream. Exclusion criteria included sunscreen ingredients not approved in the United States, non-English studies, and studies on methods to …

Synthesis Of Thermoresponsive Poly(N-Isopropyl Acrylamide) Based Core-Shell And Hollow Shell Nanogel With Tunable Core And Shell Thickness, Mohamad Hijazi, Molla R. Islam

Student Scholar Symposium Abstracts and Posters

Nanogels have emerged as a notably safer and more effective means for drug delivery, primarily due to their adjustable drug-loading capabilities. Hollow-core nanoparticles offer some unique properties that are desirable for drug delivery applications. Initially, silica core nanoparticles were synthesized using the Stöber process at different temperatures where Tetraethoxysilane (TEOS) undergoes hydrolysis in the presence of ethanol and then a condensation reaction to form silica nanoparticles. Scanning Electron Microscopy (SEM) and Optical Microscopy (OM) analysis revealed that the size of silica core particles varied with the synthesis temperature (300 nm at 30°C to 150 at 60°C). The core silica particles …

Mathematical Modeling And Examination Into Existing And Emerging Parkinson’S Disease Treatments: Levodopa And Ketamine, Gabrielle Riddlemoser

Undergraduate Honors Theses

Parkinson’s disease (PD) is the second most common neurodegenerative disease across the world, affecting over 6 million people worldwide. This disorder is characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc) due to the aggregation of α-synuclein within the brain. Patients with PD develop motor symptoms such as tremors, bradykinesia, and postural instability, as well as a host of non-motor symptoms such as behavioral changes, sleep difficulties, and fatigue. The reduction of dopamine within the brain is the primary cause of these symptoms. The main form of treatment for PD is levodopa, a precursor …

Beyond Mitragynine: Composition Survey And Stability Assessment Of Kratom Tea Ordered Via Food Delivery Platforms In Bangkok, Thailand, Yuta Tokuda, Apinya Tubtimrattana, Nat Tansrisawad, Kornvalee Meesilpavikkai, Parath Thirati

Chulalongkorn Medical Journal

Background: Kratom is a native tree to Southeast Asia. Kratom leaves have long been used medicinally and recreationally due to their stimulative and opioid-like effects attributed to high endogenous levels of mitragynine and related alkaloids. Kratom is widely consumed as tea and is now publicly sold, including on food delivery platforms, after recent decriminalization despite selling of kratom products being still considered illegal by other acts.

Objectives: To assess the formulas of kratom teas sold on Thai food delivery platform together with their consistency and the stability of refrigerated teas.

Methods: Kratom alkaloids, mitragynine and 7-hydroxymitragynine, and additive contents of …

Identification And Characterization Of Novel, Small Molecule Inhibitors Of Spermine Oxidase, Amelia Bryn Furbish

MUSC Theses and Dissertations

The major intracellular polyamines spermine and spermidine are abundant endogenous compounds that are essential for cellular growth and development. Dysregulation of polyamine metabolism has been implicated as a key mechanism of injury across multiple forms of clinically challenging pathologies. Of the enzymes within the polyamine pathway, the catabolic enzyme spermine oxidase (SMOX) is of particular interest as it is subject to induction in response to infection, neuronal excitotoxicity, ischemia, and oxidative stress. In addition to the loss of radical scavenging capabilities associated with spermine depletion, catabolism of spermine by SMOX results in the production of toxic byproducts, including H_{2 …}

An Injectable In Situ Forming Collagen/Alginate/Caso4 Composite Hydrogel For Tissue Engineering Applications: Optimization, Characterization And In Vitro Assessments, Samar A. Salim, Samar A. Salim

Nanotechnology Research Centre

In situ injectable hydrogels are effectively employed to fill irregular cavitary bone defects with initiating bone growth in targeted areas. Herein, an injectable composited hydrogel composed of collagen and alginate cross-linked in situ using different concentrations of calcium sulfate (0.15, 0.3 and 0.6%, wt./v) was synthesized. Recently, CaSO4 is frequently supported as a bone graft material for bone regeneration, owing to its biocompatibility and osteoconductive properties. Moreover, hydroxyapatite (Hap) after salinization-step by (3-Aminopropyl) triethoxysilane (APTES) was incorporated for further enhancing the osteoconductive property of injected hydrogels. All fabricated hydrogels were characterized by SEM, FTIR and XRD analyses. While physiochemical characteristics …

Smart Spectrophotometric Approaches For Estimation Of Difluprednate In Existence Of Its Synthetic Precursor And Alkaline Degradation Product; Comparative Statistical Studies And Analytical Ecological Appraisal, Heidi R. Abd El-Hadi, Basma M. Eltanany, Hala E. Zaazaa, Maya S. Eissa

Bulletin of Faculty of Pharmacy Cairo University

Scientists are currently attempting to lessen the harmful effects that chemicals and solvents have on the environment. The current work suggests four sensitive and sustainable spectrophotometric techniques for quantifying difluprednate (DIF) in presence of hydrocortisone acetate, which is a synthetic precursor of DIF, and in the presence of DIF alkaline degradation product. These methods are dual wavelength, fourier self-deconvolution, first derivative, and double divisor derivative ratio. The linearity range for all methods was 15.00-40.00 µg/mL. There is no statistically significant difference between established and reported methods, and the suggested strategies are more environmentally friendly than the reported one.

Mechanistic Investigation Of C—C Bond Activation Of Phosphaalkynes With Pt(0) Complexes, Roberto M. Escobar, Abdurrahman C. Ateşin, Christian Müller, William D. Jones, Tülay Ateşin

Research Symposium

Carbon–carbon (C–C) bond activation has gained increased attention as a direct method for the synthesis of pharmaceuticals. Due to the thermodynamic stability and kinetic inaccessibility of the C–C bonds, however, activation of C–C bonds by homogeneous transition-metal catalysts under mild homogeneous conditions is still a challenge. Most of the systems in which the activation occurs either have aromatization or relief of ring strain as the primary driving force. The activation of unstrained C–C bonds of phosphaalkynes does not have this advantage. This study employs Density Functional Theory (DFT) calculations to elucidate Pt(0)-mediated C–CP bond activation mechanisms in phosphaalkynes. Investigating the …

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 …

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 …

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, …

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. …