The rich diversity of lignin small molecules derived from podophyllotoxin, a non-covalent tubulin inhibitor isolated from the Podophyllum family, has led to the clinical development of several FDA-approved anticancer agents, including DNA topoisomerase inhibitors etoposide and teniposide. While these compounds share the same tetracyclic core, two subtle structural changes that differentiate podophyllotoxin from its DNA topoisomerase-binding analogs—the presence of 4’ methylation on the aromatic ring and stereospecific glycosylation at the C-4 hydroxyl—yield two independent mechanisms. Given the immense pharmacological importance of these two features, we sought to establish a structure-activity relationship regarding modification at C-4 on the potency, specificity, and chemical properties of podophyllotoxin. Here, we synthesized a systematic library of 24 podophyllotoxin analogs with analogous ester, carbonate, and carbamate substitutions. The antiproliferative activity and efficacy of our analogs as tubulin inhibitors was evaluated through cell viability assays, tubulin polymerization assays, computer docking models, and cell cycle analysis. Our previous efforts with esters showed that increasing C-4 bulk decreases potency against human cancer cells but insignificantly impacts cell-free assays. From our preliminary SAR, small carbocyclic carbamates at C-4 are well tolerated in cell free tubulin polymerization experiments, but large, bulky alkyl groups are less tolerated.

Poster Presentation

Session 3

2:45pm – 4:00pm
Grand Salon

Chemistry

Over the last few decades, a disconnect was exposed with how science is taught in the classroom and how it is applied within the real world. Typically, this disconnect is seen in courses like General Chemistry, which are required to build a strong foundation. These courses earn the title of “weeder courses”. While the intention is to “weed out” bad scientists/students, the courses instead leave behind historically underrepresented groups and students with less math preparation.This can create even more barriers for these students to become scientists. We designed a weekly homework assignment to remedy this disconnect between the classroom and applications. In this study, we analyze student responses for forty-four students to the weekly question “How have you observed chemistry outside of class this week?” Students were asked how they observed chemistry, not to describe the chemistry. Despite this, 51.66% of student responses included an additional explanation of why their response is an example of chemistry. During analysis of students provided additional explanations, we noticed that students tend to use more scientific language in the responses that include an additional explanation. Analysis looking at the connection between scientific language and additional explanation in NVivo 14 is currently underway. When students begin to recognize the chemistry taking place around them outside of the classroom and use scientific language to describe what they observe, it signifies a deeper connection and understanding of the material. By helping students bridge these connections, students will see that chemistry can happen anywhere, and that anyone has the ability to become a chemist.

Poster Presentation

Session 3

2:45pm – 4:00pm
Grand Salon

Chemistry

General Chemistry in post-secondary education classrooms lacks a clear connection between the traditional curriculum and real-world applications. This creates a disconnect with students’ interest and negative affect in chemistry learning. As a result, students do not feel like they belong in chemistry spaces, contributing to high DFW rates in General Chemistry.  Assignment design is one way to bridge this gap. In this study, we discuss the design and implementation of a final project in a first semester of General Chemistry course at California State University Channel Islands, a Hispanic Serving Institution. The students are tasked to present why chemistry matters to their home community. There are three phases of the project. In the planning phases, students complete a pre-survey and get feedback on topic ideas and presentation mediums. The second phase consists of a multi-draft research paper. The third phase consists of making a presentation explaining the chemistry, in a multi-draft process. A post-survey was given to students that asked their perceptions from the assignment. When asked, “Do you feel this assignment helped you better understand the role of chemistry in your life overall?”, 80% of students agreed or strongly agreed that this had an impact. By completing this final project, students understand why chemistry matters to them by making personal connections to their home community. This project aims to make students feel more confident in identifying and communicating chemistry. As a result, the students will see themselves as scientists, helping diverse students recognize that they belong in these spaces.

Poster Presentation

Session 3

2:45pm – 4:00pm
Grand Salon

Chemistry

The application of machine learning in 21st century drug discovery and design is one of the most exciting areas of contemporary biopharmaceutical R&D, promising generation of lead molecule structures with less time, less money, and greater accuracy than traditional approaches.  These promises are particularly attractive for drug development focused on the central nervous system, an area both critically in need of novel therapeutics and notoriously difficult to target, largely due to how challenging it is to design compounds that successfully pass through the blood-brain barrier (BBB) and/or the blood-cerebrospinal fluid (CSF) barrier.  In an effort to help address this obstacle, my research applies Graph Neural Networks (GNNs) to generate novel chemical compounds that can enter the BBB, the blood-CSF barrier, or both.  GNNs are deep learning algorithms designed to interpret data represented as mathematical graphs — a collection of nodes connected by edges — which are very intuitive structures to represent molecules in a computer.

Poster Presentation

Session 3

2:45pm – 4:00pm
Grand Salon

Chemistry

Without active effort from chemistry professors, students often find it difficult to make connections between the material they are learning in their general chemistry courses and the world around them. This can cause students to have difficulty achieving a deeper understanding of the material, as they are not incentivised to learn “niche” topics that might have little perceived impact on their daily lives.The design of homework assignments is one possible solution to this problem. Students in the W.M. Keck Science Department at the Claremont Colleges who were enrolled in General Chemistry I completed a homework assignment every week in which they had to respond to the question, “How have you observed chemistry outside of class this week?” Responses were qualitatively coded using NVivo 14 based on how they related to the content that was discussed in class. Analysis is currently underway, but it is anticipated that more introductory concepts will be discussed in student responses throughout the semester, while traditionally challenging topics are only going to be covered following their coverage in class. Students are given a chance each week to practice applying the knowledge they have learned by actively trying to establish connections between the material they are studying in the classroom and the outside world. If students can identify chemistry in the world around them, it no longer feels like a “niche” topic, which could incentivize them to strive for a deeper level of understanding.

Poster Presentation

Session 3

2:45pm – 4:00pm
Grand Salon

Chemistry

This research works on developing a cost-effective, reliable method to measure thin film thicknesses of non-absorbing materials such as silicon dioxide(SiO2). By doing this, the development of low-cost techniques can open pathways to democratize materials research, which tends to be prohibitively expensive. The methods involved include the characterization of high-capacitance materials and the repurposing of an available UV visible spectrometer and reflectance probe. We are taking freeware, such as OceanView from Ocean Optics, and developing a thin film characteristic technique measurement utilizing refractive indices. The system is calibrated using silicon(Si) and SiO2 thin films as a reference. As a result, we are expected to find the values to align with the actual thicknesses of the samples, but the calibrations and formulas may need adjustment for that. Future steps include using the refractive index of other materials to make films and calibrating the results using physical means, such as atomic force microscopy, at facilities like the University of California, Santa Barbara (UCSB). Once we have those references and good calibrations, we can apply the technique to other materials and further prove its viability.

Poster Presentation

Session 3

2:45pm – 4:00pm
Grand Salon

Chemistry

Since the initial success of fluorinated corticosteroids, many have been investigated for their potent anti-inflammatory activities and improved pharmacokinetic profiles. In particular, dexamethasone received FDA approval in 1958 for the treatment of inflammatory conditions like arthritis, asthma, eczema, and sclerosis. Though fluorination of corticosteroids has demonstrated elongation of metabolic half-life, dosing challenges remain where a prodrug would be useful. As glucocorticosteroids bind to the glucocorticoid receptor at the C-3 ketone, C-11 alcohol, and C-22 alcohol, modification of these locations would hinder binding to the receptor and increase the length of their metabolism. Inspired by prednisolone, a corticosteroid frequently delivered as its C-11 oxidized prodrug prednisone, we attempted a similar synthetic strategy of prodrugging through the oxidation of the secondary alcohol at C-11 into a ketone to increase the half-life of C-9 fluorinated steroids such as dexamethasone, fluocinolone acetonide, triamcinolone acetonide, betamethasone, and fludrocortisone. This prodrugging strategy is atom economical, generalizable to the 11-hydroxysteroid scaffold, and yields no potentially toxic byproducts. Additionally, the structural verification of these oxidized steroids was performed through the use of LCMS, 1H, and 19F Benchtop NMR. These compounds are currently being evaluated for catabolic dehydrogenation through HPLC, where we anticipate dehydrogenase activity by the liver enzyme 11β-hydroxysteroid dehydrogenase at the aforementioned C-11 scaffold. If successful, the library of five fluorinated steroids presented would be the first successful examples of 11-oxyfluorocorticosteroid prodrugs.

Poster Presentation

Session 2

1:00pm – 2:15pm
Grand Salon

Chemistry

Senescent cells, cells that are associated with tissue damage, cellular damage, and cancer, are linked with inflammation, tissue destruction, and various other conditions in the human body. These cells are linked with the natural aging process, therefore increasing geriatric quality of humans. To treat this, senolytic drugs, such as ARV-825, have been produced. ARV-825 is a novel senolytic bromodomain protein family (BET) inhibitor that uses proteolysis-targeting chimera technology (PROTAC). This means that ARV-825 has been engineered to cause protein degradation and apoptosis. Specifically, ARV-825  prompts apoptosis while reducing the expression of BRD4, a senescent cell marker. This specific drug aims to treat “side effect” cells that are the result of Neuroblastoma, a very common solid childhood tumor.  Due to its potency and its ability to cause protein degradation and apoptosis, ARV-825 is efficient in treating senescent cells that are a response to tumor secretions, body inflammation, and gene-impacting treatments such as chemotherapy. Planaria, specifically the Girardi sp., is a freshwater flatworm we are utilizing as a model system to test the effectiveness of ARV-825. These worms have pluripotent stem cell promoters that aid in rapid tissue regeneration.  To examine this, planaria viability was tested at different ARV-825 concentrations, resulting in a 25% survival rate in 1µM concentrations, and a 50% survival rate at concentrations 2µM-10µM. Quick tissue regeneration rates coupled with the fact that planarians share morphology and tissue function with many other animals make this species valuable to scientific research. By testing this ARV-825 in a planaria model system, as opposed to a human or mouse model, the drug’s mechanism can be tested and compared to see if these mechanisms are conserved among different organisms. This data may be used to further research the implications of ARV-825 and its efficiency in treating senolytic cells.

Poster Presentation

Session 2

1:00pm – 2:15pm
Grand Salon

Chemistry

The aim of this study is to gauge the impact a homework assignment has on students’ perception of chemistry in the world around them. The purpose of the assignment was to help bridge students’ disconnect between material taught in undergraduate chemistry courses and its real world applications. A weekly homework assignment was given to students asking, “How have you observed chemistry outside of class this week?” The data consists of responses from 173 students in a flipped, first-semester general chemistry classroom from Fall 2021 at the Keck Science Department at Scripps, Claremont McKenna, and Pitzer Colleges. NVivo 14 was used to code the responses into various categories, including “Is the Chemistry Correct?” This classification seeks to determine if the examples of chemistry provided by students in their responses were explained correctly. The results are anticipated to reflect that as students progress through the semester and become more familiar with foundational general chemistry concepts, they are more likely to correctly explain the chemistry related to the examples they provide in their responses. Analysis of this data is currently underway. The preliminary analysis reflects the anticipated increase in comfortability as students advanced through the semester. By asking students to identify chemistry outside of the classroom each week, they will begin to recognize that chemistry happens everywhere in the world around them and they will begin to see themselves as scientists. This will indicate an increase in their understanding of, and comfortability with, chemistry both inside and outside of the classroom.

Poster Presentation

Session 2

1:00pm – 2:15pm
Grand Salon

Chemistry

Pancreatic ductal adenocarcinoma (PDAC), is the most deadly pancreatic cancer because of
insufficient detection techniques. This results in delayed diagnosis and late cancer stages,
severely limiting treatment options. The current treatment for PDAC is a nucleoside analogue,
Gemcitabine, which faces several drug-resistant mechanisms that hinder its chemotherapeutic potential. We propose a nucleoside analogue with a polyethylene glycol amino (PEGA) modification. The PEGA group is also hypothesized to serve as a chelating agent for zinc and iron ions. Given the importance of iron for RNR activation and zinc homeostasis in cancer, this modification can improve the chemotherapeutic potential of the drug. We have done computational studies including molecular docking using the internal coordinate mechanics algorithm (ICM), SWISS Absorption, Distribution, Metabolism, and Excretion (SWISSADME), and prediction of activity spectra for substances (PASS), utilizing the Way2Drug online application; We have also begun synthesizing the intended compound. The edock scores, the root mean square deviation (RMSD), and the H-bonding formation were analyzed on ICM. The PEGA moiety indicated a strong binding affinity to a known substrate binding residue in the catalytic site, Asn211, a vital component of catalytic processes. The pharmacokinetics and toxicity were assessed through SWISSADME, which demonstrated excellent solubility scores of logS -0.37 and showed non-toxic interactions with CYP isoenzymes. Through PASS prediction, the biological activity of the compound showed high potential as an RNR inhibitor, with a probability of activity (Pa) to probability of inactivity (Pi) of 0.174 to 0.011. In conclusion, the proposed analogue demonstrated promising target inhibition potency for further investigation via in vivo and in vitro studies.

Poster Presentation

Session 2

1:00pm – 2:15pm
Grand Salon

Chemistry