Medicinal-Pharmaceutical Chemistry Commons^™

Study Of Modified Salinomycin Analogs On Inhibition Of Triple Negative Breast Cancer Metastasis And Invasion, Farnaz Malekmarzban

Theses and Dissertations

Triple negative breast cancer (TNBC) is a more aggressive type of breast cancer which contains faster growth, higher metastasis rate and worse prognosis. The main challenge toward treatment of this type of cancer is being heterogeneous. Recently, Salinomycin (SAL) has been considered as a potential agent for triple negative breast cancer treatment. However, chemical modification of SAL is needed to improve SAL selectivity to cations and decrease its cytotoxicity. The purpose of this study was to evaluate the effect of chemically modified analogs of SAL on the viability, metastasis, Wnt pathway as well as angiogenesis of Triple negative breast cancer …

Microencapsulation Of Cosmos Caudatus Kunth Extract Using Sodium Alginate And In Vitro Antioxidant Activity Test, Safina Samara Nur Fadlila, Oktavia Eka Puspita, Zubaidah Ningsih, Anna Safitri

Makara Journal of Science

This study aims to encapsulate Cosmos caudatus K. leaf extract in sodium alginate crosslinked with calcium chloride (CaCl₂) as coating materials through freeze-drying. Antioxidant assays were performed to evaluate the applicability of the microcapsules as antidiabetic medicines. Their characteristics, antioxidant activity, and encapsulation efficiency (EE) were also examined. Results indicated that the concentration of sodium alginate and pH influenced the manufacturing process of the microcapsules. The highest EE was obtained at pH 6 and alginate concentration of 2% (w/v). The IC₅₀ for the antioxidant activity of the microcapsules was 139.96 ± 1.094 μg/mL. Scanning electron microscopy confirmed …

Designing Dual-Responsive Drug Delivery Systems: The Role Of Phase Change Materials And Metal-Organic Frameworks., Wanying Wei, Ping Lu

College of Science & Mathematics Departmental Research

Stimuli-responsive drug delivery systems (DDSs) offer precise control over drug release, enhancing therapeutic efficacy and minimizing side effects. This review focuses on DDSs that leverage the unique capabilities of phase change materials (PCMs) and metal-organic frameworks (MOFs) to achieve controlled drug release in response to pH and temperature changes. Specifically, this review highlights the use of a combination of lauric and stearic acids as PCMs that melt slightly above body temperature, providing a thermally responsive mechanism for drug release. Additionally, this review delves into the properties of zeolitic imidazolate framework-8 (ZIF-8), a stable MOF under physiological conditions that decomposes in …

Implementing 1.5 Millimeter Internal Diameter Columns And A Portable Capillary Column Instrument Into Monoclonal Antibody Analytical Workflows, Benjamin Libert

Theses and Dissertations

Using 1.5 mm inner diameter (i.d.) columns to bridge the gap between routinely used 2.1 mm i.d. columns and capillary bore columns allows for a sequential but significant increase in performance without the need for specialized equipment associated with very low dispersion liquid chromatography (LC) systems. These 1.5 mm i.d. columns balance an increase in sensitivity compared to 2.1 mm i.d. columns (theoretically doubling the time-domain peak area in mass sensitive detectors for the same mass load), while mitigating the efficiency losses due to extra-column dispersion effects that are commonly observed with 1.0 mm i.d. columns. Here, the use of …

Integrated Computational Approaches: Elucidating Molecular Mechanisms Of Pathogenic Proteins And Designing Novel Inhibitors Against Mycobacterium Tuberculosis And Sars-Cov-2, Justin David Carbone

Theses and Dissertations

Chapter 1 introduces computational strategies in computer aided drug design (CADD), focusing on physics-based methodologies to enhance drug discovery. This chapter also discusses the theoretical foundations and practical applications of molecular dynamics (MD) simulations including free energy and stochastic kinetic analysis. In Chapter 2, CADD methods lead to development of inhibitors targeting the RNA Dependent RNA Polymerase (RdRP) of SARS-CoV-2. Inspired by the nucleotide inhibitor Molnupiravir, we aim to design a combinatorial library of 72 novel inhibitors capable of impeding a dual threat inhibition mechanism inducing lethal mutations along with stalling viral replication with specific selectivity to RdRp over Human …

Production Of The Siderophore Lysochelin In Rich Media Through Maltose-Promoted High-Density Growth Of Lysobacter Sp. 3655, Fang Zhang, Jia Liu, Lin Jiang, Yongbiao Zheng, Lingjun Yu, Liangcheng Du

Department of Chemistry: Faculty Publications

Siderophores are produced by bacteria in iron-restricted conditions. However, we found maltose could induce the biosynthesis of the siderophore lysochelin in Lysobacter sp. 3655 in rich media that are not compatible with siderophore production. Maltose markedly promoted cell growth, with over 300% increase in cell density (OD₆₀₀) when LB medium was added with maltose (LBM). While lysochelin was not detectable when OD₆₀₀ in LBM was below 5.0, the siderophore was clearly produced when OD₆₀₀ reached 7.5 and dramatically increased when OD₆₀₀ was 15.0. Coincidently, the transcription of lysochelin biosynthesis genes was remarkably enhanced following the …

Nanoparticles As Antioxidant Agents: A Comprehensive Review, Sulyman Olalekan Ibrahim, Halimat Yusuf Lukman, Fatimat Ronke Abdulkadir, Monsurat Yemisi Bello, Yusuf Oloruntoyin Ayipo, Halimah Funmilayo Babamale, Marili Funmilayo Zubair, Olubunmi Atolani

Al-Bahir

This study seeks to provide a comprehensive overview of the latest progress in the antioxidant properties of nanoparticles. Nanoparticles (NPs) have emerged as a promising tool in several domains of science and industry, including their application as antioxidant agents. The main knowledge gaps seem to be in correctly identifying the make-up of the naturally occurring phytochemicals that give these nano-antioxidants their extraordinary pharmacology and drug-like properties. In many instances, that characterization is done using spectroscopy instrumentation such as fourier-transform Infrared (FT-IR), scanning electron microscope (SEM), and X-ray diffraction analysis (XRD). From literature appraisals, it was discovered that a lot of …

Development Of Platinum(Iv)-Gold(I)-Based Anticancer Agents, Javier E. Lopez-Hernandez

Dissertations, Theses, and Capstone Projects

Heterometallic compounds have emerged as prospective multitarget anticancer drugs. These species may display improved efficacy and physicochemical properties compared to the individual metallic fragments, while helping combat drug resistance by exerting effects on multiple pathways. In this thesis we describe the synthesis of new bi- and tri-metallic compounds based on platinum(IV) compounds containing FDA-approved platinum agents, and gold(I) derivatives with known anticancer properties. We demonstrate their toxicity and selectivity against a small panel of renal, bladder, ovarian, and breast cancer cell lines, as well as their synergistic effects. We have selected a trinuclear PtAu₂compound containing the Pt(IV) core …

Examining The Authenticity Of The 'Ether Model' In Certain O-Glycosylation Reactions, Varad Vinayak Agarkar

LSU Doctoral Dissertations

Acinetobacter baumannii is a gram-negative bacterium species that is responsible for nosocomial infections. It has shown antibiotic resistance and has been designated an urgent threat by the CDC. In Chapter 1, I highlight my efforts in the synthesis of a Kdo building block in the journey towards the construction of an A. baumannii lipooligosaccharide (LOS) core pentasaccharide- a potential candidate for glycoconjugate vaccine against A. baumannii infection. I talk about various optimizations and improvements in the Kdo monosaccharide synthesis and the mechanistic insights I provided about a critical transformation in the synthetic sequence.

Chemical O-glycosylation is a significant research …

Purification And Isolation Of Α-Chloro-Β-Lactone Precursor Molecules, Matthew Ellis

Honors Projects

This research investigates the synthesis of α-chloro-β-lactone molecules, focusing on the production, isolation, and purification of two precursor compounds from chloroacetic acid and substituted benzaldehydes. While multiple methods were explored, including EDC, DIC, and DCC catalysis, DCC proved to be most effective in producing higher yields. However, challenges in purification arose due to the formation of byproducts, particularly with DCC, prompting further investigation for efficient extraction and purification techniques. DCC, however, shows a promising route for α-chloro-β-lactone synthesis, despite purification complexities.

Synthesis Of Poly-N-Methylated Peptides Against Malaria, Kaitlyn Watson

Theses & Dissertations

Malaria, a life-threatening global health concern, is primarily targeted by mainstream treatments such as artemisinin-based combination therapies, focusing on the blood stage of the disease. Primaquine, one of the few drugs active against the liver stage, faces challenges with reports of resistance in Plasmodium vivax strains and relapsing infections. With the scarcity of liver-stage-targeting drugs and increasing cases of drug-resistant malaria, the World Health Organization emphasizes the urgent need for novel therapeutic agents. Marine organisms are a rich source of new bioactive compounds, and extracts from the Antarctic Sea sponge Inflatella coelosphaeroides revealed new N-methylated peptides exhibiting promising antimalarial activity, …

Synthesis And Structure Of Curaxin Analogs, Elizabeth E. Brown

Forensic Science Master's Projects

Curaxins are small molecules that have demonstrated anti-cancer activity through the activation of p53 and inhibition of nuclear factor-kB. Curaxins interfere with DNA-histone interactions, impeding DNA repair and inducing chromatin destabilization. This leads to apoptosis through alterations in spatial genome organization and oncogene expression. The results are due to DNA binding activity. A team of researchers, including a Roswell Park Cancer Institute group, discovered these molecules. This project aims to synthesize a diverse library of novel analogs of curaxin through a modified literature protocol to enhance the chemotherapeutic potency while minimizing non-specific cytotoxicity. N-alkylation of diacetyl carbazole followed by saponification …

Design, Synthesis, And Optimization Of Allosteric Inhibitors Of Hiv-1 Integrase, Krunal H. Patel

Dissertations

The human immunodeficiency virus type 1 (HIV-1) infection remains a global health crisis, necessitating the development of innovative antiviral strategies. During the integration step, HIV-1 integrase (IN) interacts with viral DNA and the cellular cofactor LEDGF/p75 to effectively integrate the reverse transcript into the host chromatin. Recently, a novel class of antiretroviral agents called Allosteric Inhibitors of HIV-1 Integrase (ALLINI) compounds has emerged as a promising avenue in the fight against HIV-1. While originally designed to inhibit IN-LEDGF/p75 interactions, these compounds have been shown to also impact late-stage viral maturation severely through IN multimerization. Induction of IN multimerization interferes with …

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 …

Two Studies: Aromatization-Driven Ring Opening Functionalization Of Unstrained Cycloalkanones Through Visible Light Catalysis, And Synthesis Of Amino Endoperoxides Using Self-Doped Titanium Dioxide (Ti3+@Tio2) As A Photocatalyst, Enoch Kudoahor

Graduate Theses and Dissertations

The pharmaceutical industry has been focused on discovering new innovative drugs over the last decade, but the syntheses are either inefficient or the approach to environmental sustainability raises significant concerns. Photochemistry and photocatalysis have found widespread applications in organic synthesis as a result of this pressing issue. Our role as organic chemists is to improve environmental quality by creating a "greener" world through the development of efficient synthetic methods and strategies. Solar energy is now one of the most abundant and renewable natural resources. The emergence of environmental sustainability concerns has led to the development of new techniques for harnessing …

Affinity-Enhanced Microdialysis Using Covalent Organic Frameworks (Cofs) Applied To Various Non-Steroidal Anti-Inflammatory Drugs (Nsaids) And Their Metabolites, Kehinde Adedeji Olubanjo

Graduate Theses and Dissertations

Microdialysis is a valuable tool in neurosciences and pharmaceutical sciences, aiding research in drug-related areas. However, it faces a notable limitation in sampling hydrophobic analytes due to their adherence to the probe materials brought about by non-specific adsorption, thereby reducing relative recovery or overall extraction. In this work, two affinity agents, polydimethylsiloxane (PDMS) beads suspended in sodium dodecyl sulfate (SDS) surfactant and covalent organic frameworks I(COFs) were employed as affinity agents in microdialysis for the extraction of hydrophobic drugs. When PDMS beads were employed as affinity agents, at the flow rate of 1 µL/min the relative recovery of both the …

Modern Approaches To Treating Hospital Acquired Infections: An Overview Of Current Treatments Using Antibiotics And New Therapies Centered Around Photo-Activated Porphyrins, Meghan Johns

Senior Honors Theses

Annually, hospital-acquired infections (HAIs) affect hundreds of thousands of people in the U.S. and impose a great economic burden. The current problem is further exacerbated due to the failure of traditional treatment strategies considering the rise in antimicrobial resistance rates. Besides the fact that antimicrobial resistances complicates clinical treatment strategies, patients are also more vulnerable to secondary infections and complications from prolonged antibiotic use. As a result, research investigating novel treatment strategies for bacterial infections has recently increased. A strategy using porphyrin-based compounds is showing promise. Porphyrins and their derivatives have exhibited bactericidal effects against Gram-positive bacteria by the destruction …

Shared Genomic Segments Analysis Identifies Mhc Class I And Class Iii Molecules As Genetic Risk Factors For Juvenile Idiopathic Arthritis, Cecile N. Avery, Nicole D. Russell, Cody J. Steely, Aimee O. Hersh, John F. Bohnsack, Sampath Prahalad, Lynn B. Jorde

Markey Cancer Center Faculty Publications

Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease encompassing several clinically defined subtypes of varying severity. The etiology of JIA remains largely unknown, but genome-wide association studies (GWASs) have identified up to 22 genes associated with JIA susceptibility, including a well-established association with HLA-DRB1. Continued investigation of heritable risk factors has been hindered by disease heterogeneity and low disease prevalence. In this study, we utilized shared genomic segments (SGS) analysis on whole-genome sequencing of 40 cases from 12 multi-generational pedigrees significantly enriched for JIA. Subsets of cases are connected by a common ancestor in large extended pedigrees, increasing the …

Ultrasoft Platelet-Like Particles Stop Bleeding In Rodent And Porcine Models Of Trauma, Kimberly Nellenbach, Emily Mihalko, Seema Nandi, Drew W. Koch, Jagathpala Shetty, Leandra Moretti, Jennifer Sollinger, Nina Moiseiwitsch, Ana Sheridan, Sanika Pandit, Maureane Hoffman, Lauren V. Schnabel, L. Andrew Lyon, Thomas H. Barker, Ashley C. Brown

Engineering Faculty Articles and Research

Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly (N-isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed …

Accurate Characterization Of Binding Kinetics And Allosteric Mechanisms For The Hsp90 Chaperone Inhibitors Using Ai-Augmented Integrative Biophysical Studies, Chao Xu, Xianglei Zhang, Lianghao Zhao, Gennady M. Verkhivker, Fang Bai

Mathematics, Physics, and Computer Science Faculty Articles and Research

The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs in vivo, leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking. In this study, quantitative structure–kinetics relationship (QSKR) models were developed using 132 inhibitors targeting the ATP binding domain of heat shock protein 90α (HSP90α) to predict the dissociation rate …