Category Archives: poster

Mercedes DeMoss–In Vivo Screening of Indenoisoquinoline compounds

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Abstract: “The MYC oncogene is a promising drug target for cancer research due to its overexpression in a majority of cancers. However, the MYC protein is considered undruggable. The G-quadruplex structure formed in the promoter region of the MYC oncogene is a transcription inhibitor. Stabilizing the MYC promoter G-quadruplex with small molecules decreases MYC levels in cancer cells causing cell death. Indenoisoquinoline compounds have been shown to induce and stabilize the MYC promoter G-quadruplex and inhibit MYC expression. Currently, there is no commercially available DNA-targeted small molecule compound library. In this study we first establish a DNA-targeted molecule compound library with over 2000 indenoisoquinoline compounds and analogs. We created a physical library with electronic data to easily access the information about each compound. We screened the library in vitro for binding of each compound to the MYC promoter G-quadruplex. Then we used in vivo cellular assays with two different cancer cell lines to determine the compounds’ toxicity to cancer cells and their ability to stabilize the MYC promoter G-quadruplex and downregulate MYC. With these results we discovered 270 hit compounds. Currently we are conducting more detailed studies of these hit compounds to better determine their MYC promoter G-quadruplex binding and MYC inhibition in cancer cells to ultimately develop an in-depth structure-activity relationship for indenoisoquinolines at this promising cancer target.”

Text Transcript_DeMoss

Matthew Martin–Synthesis, Characterization, and Anticancer Activity of Arsenoplatin-4

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Abstract: “The FDA approved anticancer drug arsenic trioxide (As2O3) is highly efficient for treatment of acute promyelocytic leukemia, but due to its rapid renal clearance in the form of arsenous acid, As(OH)3, it has been ineffective in the treatment of solid cancers. A new class of potent anticancer agents that contain As(OH)2 moiety bound to platinum(II) center, arsenoplatins [Pt(µ-NHC(R)O)2XAs(OH)2] (R=CH3 or CH3CH2), X=Cl-, SCN-), have been synthesized. A high Pearson correlation coefficient (r = 0.96) was obtained while comparing anticancer activity of Arsenoplatin-2 (R = CH3CH2, X=Cl- ; AP-2) to As2O3 in the NCI-60 screen, suggesting the two compounds act in a similar manner. This project aims to synthesize, characterize, and test the anticancer activity of an iodide analog of AP-2, labeled AP-4. X-ray, NMR, and elemental analysis have been completed to determine the structure and purity of this new compound. The cytotoxicity of AP-4 in the triple negative breast MDA-MB-231 cancer cell line has been evaluated by MTS cell proliferation assay. Interaction of AP-4 with the biologically important molecule glutathione (GSH) was assessed by fluorescent detection assay. GSH depletion has been shown to sensitize cancer cells that are resistant to platinum drugs. The effect of AP-4 concentrations on the GSH level is discussed. Based on current results, AP-2 and AP-4 may act as a delivery vehicle for As2O3, overcoming one of the primary limitations of As2O3 as a drug for solid cancers.”

Transcript_Martin

Ji Seon “Lucy” Shon–Single-Chain Nanoparticle Delivers a Partner Enzyme for Concurrent and Tandem Catalysis in Cells

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Abstract: “In biological environment, enzymes catalyze reactions at extremely high efficiency and selectivity. The polypeptide scaffolds of enzymes selectively bind substrates to the catalytic to increase the efficiency. Single-chain nanoparticles have been developed with Ru(bpy)3 as enzyme mimic photocatalyst. They have been shown to penetrate the cell membrane and perform the reactions inside cells. More importantly, the nanoparticles can co-deliver an exogenous enzyme (beta-galactosidase) into cells and reside in endosomes. The SCNP-enzyme complex preserves their activity and perform concurrent or tandem reactions intracellularly. Therefore, the endosomes are engineered as artificial organelles, which efficiently producing fluorescent compounds or bioactive agents intracellularly.”

Shon_Text transcript

Luke Madden–Examination of Unprompted Shared Resources and Motives by Chemistry Educators during Online Discussions in Graduate Courses

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Abstract: “Everyday chemistry educators use resources relating to their curriculum to help advance student learning in the classroom. These materials can be anything from online sources, videos, or even lab experiments. Further, teachers are always looking for resources to help improve their own teaching ability and student understanding; applying different materials can be beneficial for students and the facilitator. This study looked at shared resources from practicing chemistry teachers who participated in online discussions in different graduate courses. The chemistry teachers were required to answer course discussion posts and had the opportunity, while not required, to share their own resources. The purpose of this study was to examine what was shared between the chemistry teachers and why they valued the resources enough to share. Resources were labeled in different categories based on the general purpose or characterization they fell into. For example, a resource that outlined a demonstration would be labeled. Finally, characterization of why a chemistry teacher valued and shared a resource was identified. One reason found was a teacher listing a resource as something they found helped student growth. General analysis found that the teachers largely asked for resources to improve their teaching ability and shared specific material such as labs or activities that were beneficial to students.”

Text Transcript_Madden.

Presentation Code Description

Jessica Villegas and Noah Moriarty–Design and Synthesis of Potential Antifungal Drugs

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Abstract: “Fungal infections occur when fungus invades the tissue, which can grow and affect the whole body if left untreated. The current antifungal drugs on the market often come with unwanted side effects, and drug resistance will always be a problem. This leads to the necessity for new pathways for inhibiting fungal infections. To this end, we are developing a library of new antifungal agents. An enzyme critical for life, methionine synthase, has a key difference between fungi and humans that can be exploited. An inhibitory molecule can be made to selectively target fungal methionine synthase based on this difference. Utilizing the modelling software Autodock, molecular modelling was done to develop theoretical molecules that target the fungal enzyme. Based on the theoretical modelling, a library of potential inhibitors was synthesized. These compounds were tested in an assay measuring the activity of the fungal enzyme in the presence of our compounds. To further evaluate the activity of each inhibitor, they are tested in a fungal growth assay which show zones of inhibition that prove our molecules are biologically active against fungi.”

Text Transcript_Villegas,Moriarty (1)

Kerui Xu–Avocado oil, coconut oil, walnut oil as true oil phase for ion transfer at nanoscale liquid/liquid interfaces

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Abstract: “The interface between two immiscible electrolyte solutions (ITIES), formed between an organic (oil) phase and an aqueous phase, is crucial for chemical sensing and for studying all kinds of electron transfer and ion transfer reactions. Thus, solvents are critical in electrochemical reactions at ITIES. Though numerous organic phases, including viscous ionic liquid, have been reported in the literature, the use of true oils as an organic phase has scarcely been explored. In our study, we present true oils, including avocado oil, coconut oil, and walnut oil as novel organic solvents for ITIES. We observed well-defined potential windows and sigmoidal cyclic voltammograms for ion transfer. The ion transfer rate constants were also measured at true oil-water interfaces supported at nanopipette of ∼20–60 nm in radius. Furthermore, we proposed additional insights on the effect of solvent viscosity on the ion transfer rate at the liquid/liquid interface, with the viscosity of these true oils being ∼50–70 times that of 1, 2-dichloroethane. The standard ion transfer rate constants of tetrabutylammonium that we calculated are 0.21–0.32 cm / s at these true oil-water interface. This study opens up the possibility to expand ITIES platform to explore new reactions, playing significant roles in separation science, chemical sensing, chemical synthesis, catalysis, etc.”
Acknowledgment: NSF CAREER

Text Transcript_Xu

Allyson Imfeld–Inorganic Chemistry Experiment: Formation and Properties of Copper Coordination Complexes

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Abstract: “Metal ions usually exist in the form of coordination complexes. The properties of such complexes include different colors, photo-physical characteristics, magnetics, reactivity, biological activity, and catalytic properties.(1) The biological activity of metal-ligand interactions has found many pharmaceutical, clinical and other practical applications. The experiments being presented here are part of a series of inorganic chemistry lab experiments designed to examine the solubility of metal ions and their ability to form coordination complexes. This particular lab focuses on the complex formations of copper by performing a series of color changing reactions. Four primary objectives include: i) Improve hands-on skills in how to prepare chemical solutions of specific molarities. ii) Understand how to prepare a series of Cu metal complexes in solution. iii) Observe color changes and precipitation reactions associated with complex formations, and iiii) analyze results in regards to metal-ligand formation. This lab experiment provides students with a multi-faceted look at different chemical principles including formation of coordination complexes, solubility, redox chemistry and the chemistry of transition metals.

New Laboratory Module, Why Metals and Ligands Like Each Other, Purdue, Inorganic Chemistry Laboratory, CHM342, Experiment developed in 2020.

Transcipt_AllysonImfeld

Yingqi Chen–Understanding heterogeneous reactivity of N-sulfonylimine in Multicomponent reaction using machine learning

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Abstract: “1,3,4-oxadiazole plays a crucial role in organic synthesis and medicinal chemistry due to its broad-spectrum of bioactivity as an anticancer, antimicrobial, antifungal, and antifungal pharmacological agent. However, traditional approaches of multicomponent synthesis for the synthesis of 1,3,4-oxadiazole scaffold have a few limitations such as multistep synthesis, limited substrate scope, or use of harsh reaction conditions. Among reported synthesis of 1,3,4-oxadiazole, one strategy is using four building blocks to get 1,3,4-oxadiazole in a one-pot manner utilizing multicomponent reaction approach as reported by Ramazani et al and Yudin et al. One of the key steps is an imine formation, that forms in situ from aldehyde and amine, which could be partially reversible depending upon the substrate used as well as reaction conditions. In order to overcome the limitation of the previous method, we generate a machine learning model that can interpret the chemical reactivity and reaction outcome of the desired product.”

Text transcript_Chen

Kailey Komnick–Structural-Activity Relationship Campaign Leads to a Novel Chain of Fusidic Acid with an Improved Resistance Profile

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Abstract: “Multi-drug resistant bacteria are a major threat to human health worldwide. Specifically, methicillin-resistant S. aureus (MRSA) was reported as a high priority pathogen by the World Health Organization in 2017. As a result, classes of antibiotics with efficacy against these problematic Gram-positive strains are urgently needed. Fusidic acid is a gram-positive-only antibiotic that has been used to treat MRSA infections. Although fusidic acid has been efficacious in the clinic since its introduction in the 1960s, it requires a high dosing regimen due to its high resistance frequency. Herein, we report a structural-activity relationship campaign resulting in the synthesis of the first equipotent derivatives of fusidic acid. Our derivatives show potent whole cell activity and an improved resistance profile. Lastly, our lead derivative displays improved efficacy in vivo against a fusidic acid resistant strain.”

Text Transcript_Komnick