Medicinal Chemistry and Pharmaceutics Commons^™

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Achieving Better Care In Pennsylvania By Allowing Pharmacists To Practice Pharmacy, Travis Murray

Dickinson Law Review (2017-Present)

Traditionally, state legislatures implemented Prescription Drug Monitoring Programs (“PDMPs”) to assist prescribers, pharmacists, and law enforcement in identifying patients likely to misuse, abuse, or divert controlled substances. PDMP databases contain a catalog of a patient’s recent controlled substances that pharmacies have filled, including the date, location, the quantity of medication filled, and the prescribing health care provider. Prescribers in Pennsylvania have a duty to query the PDMP before prescribing controlled substances in most clinical settings. Pharmacists have a similar duty in Pennsylvania to dispense safe and effective medication therapy to patients and to screen patients for potential signs of misuse, …

Protein Phosphatase 2a In Metformin’S Action In Primary Human Skeletal Muscle Cells, Aktham H. Mestareehi

Wayne State University Dissertations

Diabetes is a group of metabolic diseases characterized by hyperglycemia caused by defects in insulin secretion, insulin action, or both. Diabetes is associated with damage, dysfunction, and failure of various organs, such as the eyes, heart, kid-neys, and brain. Diabetes is mainly classified into type 1 (T1DM) and type 2 diabetes (T2D). Diabetes affects more than 34 million people in the USA (about 1 in 10) and more than 90% of diabetic patients have type 2 diabetes (T2D). Insulin resistance is a main characteristic feature of type 2 diabetes. Skeletal muscle insulin resistance is con-sidered to be the primary defect …

Targeted Combination Therapy Of Triple-Negative Breast Cancer, Ketki Bhise

Wayne State University Dissertations

TARGETED COMBINATION THERAPY OF TRIPLE-NEGATIVE BREAST CANCERby KETKI BHISE May 2021 Advisor: Dr. Arun Iyer Major: Pharmaceutical Sciences Degree: Doctor of Philosophy Triple Negative Breast Cancer (TNBC) accounts for 10-20% of the total breast carcinoma cases. There is no FDA-approved targeted therapy for TNBC due to lack estrogen, progesterone and HER-2. We have identified the role of a hypoxia biomarker, carbonic anhydrase IX (CAIX) in proliferation and metastasis of TNBC. Based on this observation, we have developed CAIX-targeted Doxorubicin (Dox) prodrug, abbreviated as DoxAtz. To improve the delivery of DoxAtz to the tumor, we developed long circulating liposomes (LipoDoxAtz) and …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Structure Based Prediction Of A Novel Gpr120 Antagonist Based On Pharmacophore Screening And Molecular Dynamics Simulations, Ajay Pal Mr, James Curtin, Gemma K. Kinsella

Articles

The G-protein coupled receptor, GPR120, has ubiquitous expression and multifaceted roles in modulating metabolic and anti-inflammatory processes. Recent implications of its role in cancer progression have presented GPR120 as an attractive oncogenic drug target. GPR120 gene knockdown in breast cancer studies revealed a role of GPR120-induced chemoresistance in epirubicin and cisplatin-induced DNA damage in tumour cells. Higher expression and activation levels of GPR120 is also reported to promote tumour angiogenesis and cell migration in colorectal cancer. Some agonists targeting GPR120 have been reported, such as TUG891 and Compound39, but to date development of small-molecule inhibitors of GPR120 is limited. …

Valorization Of Xylan In Agroforestry Waste Streams, Harrison Appiah

Graduate Theses, Dissertations, and Problem Reports (ETD)

Valorization of Xylan in Agroforestry Waste Streams.

Harrison Appiah

Microwave-assisted deep eutectic solvent and gamma-valerolactone metallic chloride catalyzed conversion of xylan to furfural were investigated using a 2x3 factorial experimental design at two levels of percent microwave power, reaction time, and catalyst concentration. The levels of each factor studied were (20%, 60% microwave power, 2, 4 minutes, and 10, 20mg) respectively. The effect of three metallic chloride catalysts (LiCl, FeCl3.6H20, CuCl2) on the conversion of xylan to furfural was also investigated. The gamma-valerolactone-ferric chloride sent system exhibited the highest mean yield of furfural (56.50%). The next highest furfural yield of …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Lemongrass (Cymbopogon Citratus) Ethanolic Extract Exhibited Activities That Inhibit -Glucosidase Enzymes And Postprandial Blood Glucose Elevation, Maria Dewi Puspitasari Tirtaningtyas Gunawan Puteri, Felicia Melissa Tjiptadi, Phebe Hendra, Filiana Santoso, Zalinar Udin, Nina Artanti, Florence Ignatia Florence Ignatia

Makara Journal of Science

Lemongrass is a common ingredient in Indonesian traditional herbal medicine that potently inhibits carbohydrate hydrolysis. In this study, the in vitro α-glucosidase inhibitory (AGI) activity of lemongrass was compared with its in vivo activity to retard postprandial blood glucose elevation, and the bioactive compounds responsible for these activities were observed. Both water and ethanolic extracts of lemongrass (WLG and ELG, respectively) were tested in vitro for its inhibition of the sucrose and maltose hydrolyzing activities of rat intestinal glucosidase. ELG was observed to exert higher inhibitory activities (Sucrase IC₅₀ = 8.74 mg/mL; Maltase IC₅₀ = 18.93 mg/mL) than …

Antiparasitic Peptide From The Ocean: Discovery, Synthesis And Structure-Activity Relationship Study, Kh Tanvir Ahmed

Electronic Theses and Dissertations

Millions of people die every year because of infectious diseases, and malaria is among the top five of the deadliest infectious disease. In 2018, malaria took more than four hundred thousand lives, and more than half of them are children under five years of age. Most malaria-affected parts of the world are also the home of the most underprivileged people. Seemingly, antimalarial drug discovery never achieved the attraction that it requires. Like malaria, another infectious disease that is not extensively explored by drug discovery campaigns is American trypanosomiasis or Chagas disease. More than a hundred years have passed since discovering …

Long-Acting Nanoformulated Antivirals For The Treatment And Prevention Of Hiv-1 And Hbv Infections, Dhruvkumar M. Soni Dr.

Theses & Dissertations

While antiretroviral therapy (ART) has revolutionized treatment and prevention of human immunodeficiency virus type one (HIV-1) infection, regimen adherence, viral mutations, drug toxicities, stigma and pill fatigue are limitations. These have led to the development of long acting (LA) ART. These include, but are not limited to, implantable devices, new chemical entities, prodrug modifications and nanoformulations. To these ends, this thesis focues on the transformation of nucleoside reverse transcriptase inhibitors (NRTIs) into LA parenterals, While elusive, data from our laboratories demonstrated that modifications to the PROdrug and nucleoTide technology (ProTide) enables improvements in drug apparent half-life and tissue and cell …

Acknowledgment Of Reviewers, Lily Chiu

Journal of Food and Drug Analysis

No abstract provided.

The Analytical And Biomedical Applications Of Carbon Dots And Their Future Theranostic Potential: A Review, Sukunya Ross, Ren-Siang Wu, Shih-Chun Wei, Gareth M. Ross, Huan-Tsung Chang

Journal of Food and Drug Analysis

In recent years, carbon dots (C-dots) have gained appreciable interest owing to their unique optical properties, including tunable fluorescence, stability against photobleaching and photoblinking, and strong fluorescence. Simple and low-cost hydrothermal and electrochemical approaches have been widely used in the preparation of biocompatible and high-quality C-dots. Various C-dots have been used for the quantitation of small analytes, mostly based on analyte induced fluorescence quenching. Depending on the nature of precursors, synthetic conditions (such as reaction temperature and time), and surface conjugation, multi-function C-dots can be prepared and used in diagnostics and therapeutics. Their strong fluorescence and photostability, enables use in …

Nanomaterial-Based Adsorbents And Optical Sensors For Illicit Drug Analysis, Chun-Hsien Chen, Chun-Chi Wang, Po-Yun Ko, Yen-Ling Chen

Journal of Food and Drug Analysis

The abuse of illicit drugs has been prevalent in recent years and is associated with crime and public health issues. To strengthen public security and fortify public health services with respect to the increasing severity of drug abuse, academic and government institutes have been devoted to constructing relative analytical methods for illicit drugs. To date, the development of sensors has been greatly emphasized due to their features of high sensitivity, prompt detection and flexible manipulation; thus, sensors can serve as alternatives to conventional sophisticated instruments. Recently, the use of nanomaterials has inspired the development of a series of innovative sample …

Gold Nanoparticle-Based Colorimetric And Electrochemical Sensors For The Detection Of Illegal Food Additives, Li Li, Ming Zhang, Wei Chen

Journal of Food and Drug Analysis

Lately, scandals associated with the illegal addition of poisonous chemicals to food for commercial interests have been gradually disclosed to the public. Problems related to food safety do not only harm public health but also affect the stability of economic and social development. Food safety has become a common issue in society, and strengthening the related regulations have become increasingly important. Although conventional techniques are accurate and sensitive in the detection of the vast majority of illegal food additives, they rely on time-consuming, labor-intensive procedures that depend on expensive instruments. Thus, efficient and rapid identification of poisonous, illegal additives in …

Improved Food Additive Analysis By Ever-Increasing Nanotechnology, Jing Zhang, Shui Hu, Yi Du, Ding Cao, Guirong Wang, Zhiqin Yuan

Journal of Food and Drug Analysis

Improper use of food additives may lead to potential threat to human health, making it important to develop sensitive and selective method for the detection of them. Nanomaterials with unique chemical and electrochemical properties show extensive applications in the design of food additive sensing systems. In this review, we summarize the recently adopted electrochemical and optical analysis of food additives based on nanomaterials. Detection of typical food additives (colorants and preservatives) by using different sensing mechanisms and strategies are provided. In addition, determination of illegal food additives is also briefly introduced. Finally, this review highlights the challenges and future trend …

Electrowetting-On-Dielectric (Ewod): Current Perspectives And Applications In Ensuring Food Safety, Snigdha Roy Barman, Imran Khan, Subhodeep Chatterjee, Subhajit Saha, Dukhyun Choi, Sangmin Lee, Zong-Hong Lin

Journal of Food and Drug Analysis

Digital microfluidic (DMF) platforms have contributed immensely to the development of multifunctional lab-on-chip systems for performing complete sets of biological and analytical assays. Electrowetting-on-dielectric (EWOD) technology, due to its outstanding flexibility and integrability, has emerged as a promising candidate for such lab-on-chip applications. Triggered by an electrical stimulus, EWOD devices allow precise manipulation of single droplets along the designed electrode arrays without employing external pumps and valves, thereby enhancing the miniaturization and portability of the system towards transcending important laboratory assays in resource-limited settings. In recent years, the simple fabrication process and reprogrammable architecture of EWOD chips have led to …

Nanomaterial-Based Fluorescent Biosensor For Veterinary Drug Detection In Foods, Xiaoqi Tao, Yuanyuan Peng, Juewen Liu

Journal of Food and Drug Analysis

Veterinary drugs have been widely used in the food industry. Their residues in food products need to be tightly regulated to ensure food safety. In particular, some veterinary drugs are still used illegally, although they have already been banned. Nanomaterials are playing an increasingly important role in analytical chemistry due to their unique properties. Compared to traditional organic dyes and colloidal gold nanoparticle labels, fluorescent nanomaterials appear particularly attractive for the detection of veterinary drug residues. This review summarizes recent advancements of fluorescent biosensors using nanomaterials for the detection of veterinary drug residues in foods. The useful properties of each …

Carbon Quantum Dots For The Detection Of Antibiotics And Pesticides, Han-Wei Chu, Binesh Unnikrishnan, Anisha Anand, Yang-Wei Lin, Chih-Ching Huang

Journal of Food and Drug Analysis

Carbon quantum dots (CQDs) are novel nanomaterials with interesting physical and chemical properties, which are intensely studied only in the last decade. Unique properties, such as its inherent fluorescent property, high resistance to photobleaching, high surface area, ease of synthesis, flexible choice of precursor, and surface tunability enable CQDs for promising application in biosensing. Therefore, it is highly useful in clinical, forensic, medical, food and drug analyses, disease diagnosis, and various other fields of biosensing. In addition, their fluorescence properties are tunable by the interaction with certain molecules via different mechanisms, which enables their application for sensing of those molecules, …

Noble Metal Nanomaterial-Based Aptasensors For Microbial Toxin Detection, Yue He, Cong-Ying Wen, Zhi-Jun Guo, Yu-Fen Huang

Journal of Food and Drug Analysis

Microbial toxins generated by bacteria, fungi and algae cause serious food-safety problems due to the frequent contamination of foodstuffs and their poisonous nature. Becoming acquainted with the contamination condition of foodstuffs is highly dependent on developing sensitive, specific, and accurate methods for targeting microbial toxins. Aptamers, obtained from systematic evolution of ligands by exponential enrichment (SELEX), have significant advantages for microbial toxin analysis, such as small size, reproducible chemical synthesis, and modification, as well as high binding affinity, specificity, and stability. Besides, aptamers have a predictable structure and can be tailored using biomolecular tools (e.g., ligase, endonuclease, exonuclease, …