Medicinal and Pharmaceutical Chemistry Commons^™

Comparative Estimation Of The Cytotoxic Activity Of Different Parts Of Cynara Scolymus L.: Crude Extracts Versus Green Synthesized Silver Nanoparticles With Apoptotic Investigation, Shady Swidan, Amgad Khedr, Abdelaziz Farrag, Ali Nasr, Mohamed Nafie, Maged Abdel-Kader, Marwa Goda, Jihan Badr, Reda Abdelhameed

Pharmacy

Different parts of Cynara scolymus L. and their green synthesized eco-friendly silver nanoparticles (AgNPs) were screened for their cytotoxicity and apoptotic activity. Results showed that flower extract AgNPs exhibited more potent cytotoxicity compared to the normal form against PC-3 and A549 cell lines with IC50 values of 2.47 μg/mL and 1.35 μg/mL, respectively. The results were compared to doxorubicin (IC50 = 5.13 and 6.19 μg/mL, respectively). For apoptosis-induction, AgNPs prepared from the flower extract induced cell death by apoptosis by 41.34-fold change and induced necrotic cell death by 10.2-fold. Additionally, they induced total prostate apoptotic cell death by a 16.18-fold …

Novel Drugs Approved In 2021-2022, Michael Do, Bona Shin, Elaina Lioudis, Emaleigh Munn

Transformative Medicine

This article provides an abbreviated overview of the newly Federal Drug Administration (FDA)approved novel drugs of 2021-2022 with their respective approved indication(s). The FDA serves as the governing body that regularly evaluates and approves medications that will eventually be introduced to the market for routine use. These medications include both drugs that are the same or related to previously approved products (e.g., Extended indications of priorly approved medications) and novel drugs. By definition, a novel drug is an innovative product which serves to improve quality care in patient populations with unmet or advanced medical needs to overall advance patient care …

Silver Nanoparticles Formulation Of Flower Head’S Polyphenols Of Cynara Scolymus L.: A Promising Candidate Against Prostate (Pc-3) Cancer Cell Line Through Apoptosis Activation, Shady Swidan, Amgad Khedr, Marwa Goda, Abdelaziz Farrag, Ali Nasr, Mohamed Nafie, Maged Abdel-Kader, Jihan Badr, Reda Abdelhameed

Pharmacy

Cynara scolymus L. (Family: Compositae) or artichoke is a nutritious edible plant widely used for its hepatoprotective effect. Crude extracts of flower, bract, and stem were prepared and evaluated for their in vitro antioxidant activity and phenolic content. The flower crude extract exhibited the highest phenolic content (74.29 mg GAE/gm) as well as the best in vitro antioxidant activity using total antioxidant capacity (TAC), ferric reducing antioxidant power (FEAP), and 1,1-diphenyl-2-picrylhyazyl (DPPH) scavenging assays compared with ascorbic acid. Phenolic fractions of the crude extracts of different parts were separated and identified using high-performance liquid chromatography HPLC-DAD analysis. The silver nanoparticles …

Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …

Nanotherapeutics And Hiv: Four Decades Of Infection Canvass The Quest For Drug Development Using Nanomedical Technologies, Bhupender S. Chhikara, Nirpendra Singh, Poonam, Parveen Bazard, Rajender S. Varma, Keykavous Parang

Pharmacy Faculty Articles and Research

We have seen four decades of human struggle to cure or eradicate HIV infection since the first clinical detection of HIV infection. Various developed drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, microbicides, and others have known restrictions, such as side effects and resistance development when used alone, and hidden reservoir of the virus, which have opened the gates for the involvement of nanomedicine associated systems, particularly for latent sites of HIV infection. The nanotechnological vehicles, such as liposomes, dendrimers, metal nanoparticles, polymeric nanocapsules/particles, surfactants, and targeted vehicles have become part …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

10-Minute Ebd: Stimulant Medications, Rampant Caries, And Prevention, Madison Thomas Bs, Nancy Poznick Dds, Melanie E. Mayberry Dds, Ms-Hcm

The Journal of the Michigan Dental Association

The 10-Minute Evidence-Based Dentistry Column illustrates how to implement the evidence-based dentistry search process to quickly identify and apply the best literature to answer a clinical question. Through critical appraisal, the author of this article answers the clinical question of a connection between stimulant medications, rampant caries, and prevention, with a focus on the impact of ADHD medication on oral health. The term "meth mouth" often associated with dental decay is discussed in the context of xerostomia (dry mouth), a common side effect of stimulant medications. The article uses the PICO (Population, Intervention, Comparison, Outcome) system to formulate a research …

Jatropha Tanjorensis A Flora Of Southeast Nigeria: Isolation And Characterization Of Naringenin And Validation Of Bio-Enhanced Synergistical Activity Of Α- Tocopherol Toward Clinical Isolates Of Resistant Bacterial, Ikechukwu Kingsley Ijoma, Vincent Ishmael Egbulefu Ajiwe

Makara Journal of Science

Jatropha tanjorensis is among the rich floras of Southeast Nigeria and used by ethnic people to treat infections and manage health conditions. Ethnomedicine has long been employed in the treatment of ailments caused by bacterial pathogens. Studies showed that the incorporation of synthetic α-tocopherol to an antibacterial agent improves its activity. However, knowledge about the antibacterial-enhanced activity of plant-based α-tocopherols, especially those isolated from Jatropha tanjorensis, is limited because of the different bioactivities of synthetic and natural α-tocopherols. To determine the phytochemicals in J. tanjorensis, we carried out the structural elucidation of its leaf extracts. Naringenin and α-tocopherol …

Channelopathy Of Small- And Intermediate-Conductance Ca2+-Activated K+ Channels, Young-Woo Nam, Myles Downey, Mohammad Asikur Rahman, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca²⁺-activated K⁺ (K_Ca2.x/K_Ca3.1 also called SK/IK) channels are gated exclusively by intracellular Ca²⁺. The Ca²⁺ binding protein calmodulin confers sub-micromolar Ca²⁺ sensitivity to the channel-calmodulin complex. The calmodulin C-lobe is constitutively associated with the proximal C-terminus of the channel. Interactions between calmodulin N-lobe and the channel S4-S5 linker are Ca²⁺-dependent, which subsequently trigger conformational changes in the channel pore and open the gate. KCNN genes encode four subtypes, including KCNN1 for K_Ca2.1 (SK1), KCNN2 for K_Ca2.2 (SK2), KCNN3 for K …

Channelopathy Of Small- And Intermediate-Conductance Ca2+-Activated K+ Channels, Young-Woo Nam, Miles Downey, Mohammad Asikur Rahman, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca²⁺-activated K⁺ (K_Ca2.x/K_Ca3.1 also called SK/IK) channels are gated exclusively by intracellular Ca²⁺. The Ca²⁺ binding protein calmodulin confers sub-micromolar Ca²⁺ sensitivity to the channel-calmodulin complex. The calmodulin C-lobe is constitutively associated with the proximal C-terminus of the channel. Interactions between calmodulin N-lobe and the channel S4-S5 linker are Ca²⁺-dependent, which subsequently trigger conformational changes in the channel pore and open the gate. KCNN genes encode four subtypes, including KCNN1 for K_Ca2.1 (SK1), KCNN2 for K_Ca2.2 (SK2), KCNN3 for K …

Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg

All Faculty Scholarship for the College of the Sciences

C-fused γ-lactam-lactones are resident in several bioactive molecules, including anticancer agents such as omuralide. In this embodiment, we report mild conditions for the catalytic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids. The use of dichloromethane as the solvent and Ph₃PS as the catalyst led to predominant 6-endo-trig cyclization and furnished the trans-fused-γ-lactam-δ-lactones. The transformation is modular, regioselective, chemoselective, and diastereoselective. The γ-lactam-δ-lactones bear angular quaternary benzylic stereocenters, which is noteworthy since the presence of a quaternary carbon in bioactive small molecules often promotes an element of conformational restriction that imparts potency, selectivity, and metabolic stability. The …

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 was …

Design, Synthesis, And Biological Investigation Of Pyridine Sulfones As Anti-Chlamydia Trachomatis Agents, Mohamed A. Seleem

Theses & Dissertations

Chlamydia trachomatis is the most prominent cause of sexually transmitted bacterial infections worldwide, with around 128 million reported cases annually. This pathogen can cause severe urogenital and ocular consequences, resulting in infertility and trachoma. In its unique developmental cycle, Chlamydia fluctuates between two distinct forms, elementary bodies (EBs) and reticulate bodies (RBs). We hypothesized that caseinolytic protease P (ClpP), a conserved protease among bacterial species, drives the Chlamydia developmental cycle. Earlier work by the Ouellette group demonstrated that Chlamydia relies on its ClpP2 paralogue (ctClpP2) to differentiate between its developmental forms. Dysregulation of ctClpP2 had a significant …

Synthesis Of Fluorinated Ketones For Biological Evaluation At The Gaba-B Receptor, Katherine Kreusel

Honors Theses

The proper functioning of the CNS depends on the balance between excitatory and inhibitory neurotransmitters. While excitation is primarily regulated by glutamate, inhibition is regulated by γ-aminobutyric acid (GABA). When GABA binds to a GABA receptor, there is a block in nerve transmission which is important when studying pain and drug addiction. There are two types of GABA receptors that are used as drug targets: GABA-A and GABA-B. While GABA-A receptors are ionotropic and ligand-gated ion channels, GABA-B receptors are G-protein coupled receptors that are used by cells to convert extracellular signals into intracellular responses. Although many therapeutics modulate the …

Amphiphilic Cyclic Cell-Penetrating Peptides Containing Tryptophan And Arginine As Anticancer Agents And Drug Delivery System, Khalid Zoghebi

Pharmaceutical Sciences (PhD) Dissertations

Amphiphilic cyclic cell-penetrating peptides composed of an increasing number of alternative tryptophan (W) and arginine (R) were synthesized and evaluated as a molecular transporter and for their ability to deliver doxorubicin (Dox) and large molecular weight molecules, such as siRNA and proteins. We prepared a cyclic peptide containing alternative tryptophan (W) and arginine (R) residues and a lysine containing a free side chain amino group. Cyclic peptide [(WR)8WK βA] was conjugated through the free side chain amino group of β-alanine with Dox via a glutarate linker to afford [(WR)8WK]bA-Dox conjugate. The conjugate inhibited the cell viability of ovarian adenocarcinoma (SK-OV-3) …

Integration Of Medicinal Fungi Into The Heber W. Youngken Jr. Medicinal Garden, Anthony Makashov

Senior Honors Projects

The Heber W. Youngken Jr. Medicinal Garden is a one-of-a-kind resource that houses close to 300 medicinal plants and is filled to the brim with educational opportunities. For the College of Pharmacy, this garden has been the centerpiece of many classes taught here at the University of Rhode Island and has roots as a physical teaching space. While the garden contains a plethora of plant species, medicinal fungi have yet to have been included in the garden, despite their relevance as both sources of pharmaceutical drug discovery and as natural products with inherent physiological benefits themselves. The purpose of my …

Multimodal Approach To Chronic Pain Management And Prevention Of Opioid Use Disorder, Hannah Elston

The Eleanor Mann School of Nursing Undergraduate Honors Theses

Background. Chronic pain (CP) is a major public health problem that affects one-third of the population and can interfere with the activities of daily life and cause decreased quality of life. Patients with CP have been increasingly prescribed opioids, contributing to the rise in the opioid epidemic. Due to the long-term nature of CP, the use of opioids as the sole treatment for CP can cause tolerance and increased dosages overtime which can lead to addiction and potentially overdose. Therefore, CP treatment should include multimodal approaches to treatment to prevent opioid misuse, opioid use disorder (OUD), and overdose. Multimodal treatments …

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

The opioid epidemic impacted over 12 million Americans in 2019. Although they are effective pain-relieving medications, they carry addictive and dangerous side effects. Opioids, like morphine, bind non-selectively in both central and peripheral tissues; however, dangerous side effects result from central activation. Inflamed conditions of injured tissues have a lower pH (pH=6-6.5) environment than healthy central tissue (pH=7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using computationally-based molecular extension and dissection techniques. Binding to the mu-opioid receptor (MOR) is dependent on protonation of the biochemically active amine group of morphine. Fluorination of a carbon …

Nanoparticles For Biomedical Applications, Joseph Kim

Dissertations and Theses (Open Access)

This thesis presents development and evaluation of the potential of three new nanoparticles for biomedical applications. With the rapid growth of the field of nanoscience, researchers have explored developing nanoparticles for various biomedical applications, including imaging, therapy, and drug delivery. This thesis demonstrates the development of two C­₆₀ fullerene based nanoparticles and one boron based nanoparticle to answer key questions related to their biological potential.

In the first part of the thesis, we describe synthesis and characterization of a pure boron nanoparticle containing asolectin phospholipid-based liposome construct prepared using a water-in-oil emulsion method, as a novel alternative agent for …