Synthesis, Development, and Exploration of Two Small Molecule Scaffolds Toward Discovery of Novel and Potent Inhibitors of the Hypoxia-Inducible Factor-1 Pathway

The hypoxia inducible factor 1 (HIF-1) is an important transcription factor for cell survival in low oxygen concentrations. A variety of methods have been employed to selectively target this HIF pathway toward cancer therapies. A certain benzopyran-based scaffold, of lead compounds KCN1 and 64b, has been further explored to gain insights into the mode of action of those inhibitors. Utilizing established small molecule inhibitors as leads, novel inhibitors have been designed with improved potency and solubility, while only requiring two to five steps for synthesis. Qualitative structure-activity relationships developed in this work have contributed to the scientific development of other, even more therapeutically relevant small molecule inhibitors

Bonner Ferguson Data for JCST manuscript 2024.xlsx

We sought to determine if there are any differences in changes of student attitudes before and after 3.5-week and 7-week condensed flipped Organic Chemistry I courses using the Attitude toward the Subject of Chemistry Inventory Version 2 (ASCIv2). We also compared student performance for both course lengths as measured by exam and overall course grades. The results indicate that student attitudes started and remained more negative in a 3.5-week course than the 7-week course, even though exam and course grade averages are not significantly different between the formats. </p

Data_Sheet_1_Ungrading in organic chemistry: students assessing themselves and reflecting on their learning.pdf

The focus on grades has diminished the focus on learning. One strategy that aims to return students’ attention to what they are actually learning (and not just earning) is ungrading. Ungrading is thought of as any strategy in which instructors do not assign a number or letter grade to students’ assignments and assessments. Instead, faculty may (1) provide thorough feedback and engage in dialogue with students about their work, and perhaps, (2) allow students to assign their own grade. Whichever style of ungrading they choose, the scholars that have been forging the path for ungrading come from a variety of fields and perspectives, including STEM instructors in more recent years. The focus on incorporating ungrading practices into the organic chemistry curriculum provided here is adapted from a variety of practitioners, and especially the foundational work of chemistry professor Clarissa Sorensen-Unruh. In addition to discussing the current ungrading practices in various fields, we will use this perspective article to share our own experience with and lessons learned from beginning to incorporate ungrading in the undergraduate organic chemistry curriculum, both as it relates to the implementation of the practice and our own perceptions of the student experience and learning outcomes. Ultimately, the goal is to allow students to see the significance of the process of learning and to engage in some metacognitive work that they can apply to different assignments, whether in our class or not. If we want students to focus on learning, perhaps they should do the grading themselves.</p

Design and synthesis of benzopyran-based inhibitors of the hypoxia-inducible factor-1 pathway with improved water solubility

<p>While progress has been made in treating cancer, cytotoxic chemotherapeutic agents are still the most widely used drugs and are associated with severe side-effects. Drugs that target unique molecular signalling pathways are needed for treating cancer with low or no intrinsic toxicity to normal cells. Our goal is to target hypoxic tumours and specifically the hypoxia inducible factor (HIF) pathway for the development of new cancer therapies. To this end, we have previously developed benzopyran-based HIF-1 inhibitors such as arylsulfonamide KCN1. However, KCN1 and its earlier analogs have poor water solubility, which hamper their applications. Herein, we describe a series of KCN1 analogs that incorporate a morpholine moiety at various positions. We found that replacing the benzopyran group of KCN1 with a phenyl group with a morpholinomethyl moiety at the para positions had minimal effect on potency and improved the water solubility of two new compounds by more than 10-fold compared to KCN1, the lead compound.</p