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Ethyl 2-[(2-oxo-2H-chromen-6-yl)­oxy]acetate, C13H12O5, a member of the pharmacologically important class of coumarins, crystallizes in the monoclinic C2/c space group in the form of sheets, within which mol­ecules are related by inversion centers and 21 axes. Multiple C—H⋯O weak hydrogen-bonding inter­actions reinforce this pattern. The planes of these sheets are oriented in the approximate direction of the ac face diagonal. Inter­sheet inter­actions are a combination of coumarin system π–π stacking and additional C—H⋯O weak hydrogen bonds between ethyl acet­oxy groups. [ABSTRACT FROM AUTHOR]

A primary motivation for this study was to compare student perceptions and performance within a virtual learning environment to the traditional in-person learning experience for the General Chemistry II course taught during a 5-week summer session at Xavier University of Louisiana, a minority serving institution. The authors present quantitative and qualitative analyses including the comparison of student performance on exams during the COVID-19 remote learning experience with exam performance over a 3-year period of conventional in-person instruction. In this article, student grades, survey feedback, and learning outcomes are outlined. This study was performed to assist the faculty in improving and enriching the course content and its delivery, as they coped with the transition to a virtual learning environment imposed by the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) accounts for about 85‐90% of lung cancer cases, and is the number one killer among cancers in the United States. The majorities of lung cancer patients do not respond well to conventional chemo‐ and/or radio‐therapeutic regimens, and have a dismal 5‐year survival rate of ∼15%. The recent introduction of targeted therapy and immunotherapy gives new hopes to NSCLC patients, but even with these agents, not all patients respond, and responses are rarely complete. Thus, there is still an urgent need to identify new therapeutic targets in NSCLC and develop novel anti‐cancer agents. Sphingosine kinase 2 (SphK2) is one of the key enzymes in sphingolipid metabolism. SphK2 expression predicts poor survival in NSCLC patients, and is associated with Gefitinib‐resistance. In this study, the anti‐NSCLC activities of ABC294640, the only first‐in‐class orally available inhibitor of SphK2, were explored. The results obtained indicate that ABC294640 treatment causes significant NSCLC cell apoptosis, cell cycle arrest and suppression of tumor growth in vitro and in vivo. Moreover, lipidomics analyses revealed the complete signature of ceramide and dihydro(dh)‐ceramide species in the NSCLC cell‐lines with or without ABC294640 treatment. These findings indicate that sphingolipid metabolism targeted therapy may be developed as a promising strategy against NSCLC. [ABSTRACT FROM AUTHOR]

Background and purpose: Xavier University of Louisiana is a historically Black and Catholic university that is nationally recognized for its science, technology, engineering and mathematics (STEM) curricula. Approximately 73% of Xavier's students are African American, and about 77% major in the biomedical sciences. Xavier is a national leader in the number of STEMmajors who go on to receiveM.D. degrees and Ph.D. degrees in science and engineering. Despite Xavier's advances in this area, African Americans still earn about 7.5% of the Bachelor's degrees, less than 8% of the Master's degrees, and less than 5% of the doctoral degrees conferred in STEM disciplines in the United States. Additionally, although many well-prepared, highly-motivated students are attracted by Xavier's reputation in the sciences, many of these students, though bright and capable, come from underperforming public school systems and receive substandard preparation in STEM disciplines. The purpose of this article is to describe how Xavier works to overcome unequal education backgrounds and socioeconomic challenges to develop student talent through expanding biomedical training opportunities and build on an established reputation in science education. Program and key highlights: The National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS)-funded BUILD (Building Infrastructure Leading to Diversity) Program at Xavier University of Louisiana, Project Pathways, is a highly-innovative program designed to broaden the career interests of students early on, and to engage them in activities that entice them to continue their education towards biomedical research careers. Project strategies involve a transformation of Xavier's academic and non-academic programs through the redesign, supplementation and integration of academic advising, tutoring, career services, personal counseling, undergraduate research training, faculty research mentoring, and development of new biomedical and research skills courses. The Program also focuses on mentor training and providing faculty members with opportunities to improve their teaching skills as well as their research competitiveness. In addition to the wide range of activities supported by BUILD within the institution, Xavier University is partnering with a number of major research universities across the nation to achieve Project Pathways' goals. Implications: The strategies developed by Project Pathways are designed to address the challenges and barriers Xavier students face as they work towards graduate studies and entering the biomedical workforce. Xavier University of Louisiana has a long history of providing high quality, rigorous education to African American students in a very supportive environment with highly dedicated faculty and staff. The program highlighted here could be used by other institutions as a model program for assisting students in STEM and other biomedical fields of study to successfully matriculate through college and graduate school and develop their research careers. [ABSTRACT FROM AUTHOR]

1. The polycyclic hydrocarbons (PAHs), pyrene, 1-hydroxypyrene, 1-nitropyrene and 1-acetylpyrene, were found to induce Type I binding spectra with human cytochrome P450 (P450) 2A13 and were converted to various mono- and di-oxygenated products by this enzyme. 2. Pyrene was first oxidized by P450 2A13 to 1-hydroxypyrene which was further oxidized to di-oxygenated products, i.e. 1,8- and 1,6-dihydroxypyrene. Of five other human P450s examined, P450 1B1 catalyzed pyrene oxidation to 1-hydroxypyrene at a similar rate to P450 2A13 but was less efficient in forming dihydroxypyrenes. P450 2A6, a related human P450 enzyme, which did not show any spectral changes with these four PAHs, showed lower activities in oxidation of these compounds than P450 2A13. 3. 1-Nitropyrene and 1-acetylpyrene were also found to be efficiently oxidized by P450 2A13 to several oxygenated products, based on mass spectrometry analysis. 4. Molecular docking analysis supported preferred orientations of pyrene and its derivatives in the active site of P450 2A13, with lower interaction energies (Uvalues) than observed for P450 2A6 and that several amino acid residues (including Ala-301, Asn-297 and Ala-117) play important roles in directing the orientation of these PAHs in the P450 2A13 active site. In addition, Phe-231 and Gly-329 were found to interact with pyrene to orient this compound in the active site of P450 1B1. 5. These results suggest that P450 2A13 is one of the important enzymes that oxidizes these PAH compounds and may determine how these chemicals are detoxicated and bioactivated in humans. [ABSTRACT FROM AUTHOR]

With the widespread use of O-alkoxyresorufin dealkylation assays since the 1990s, thousands of inhibitors of cytochrome P450 family 1 enzymes (P450s 1A1, 1A2, and 1B1) have been identified and studied. Generally, planar polycyclic molecules such as polycyclic aromatic hydrocarbons, stilbenoids, and flavonoids are considered to potentially be effective inhibitors of these enzymes, however, the details of the structure-activity relationships and selectivity of these inhibitors are still ambiguous. In this review, we thoroughly discuss the selectivity of many representative P450 family 1 inhibitors reported in the past 20 years through a meta-analysis. [ABSTRACT FROM AUTHOR]

The cytochrome P450 (CYP) superfamily of heme enzymes play an important role in the metabolism of a large number of endogenous and exogenous compounds, including most of the drugs currently on the market. Inhibitors of CYP enzymes have important roles in the treatment of several disease conditions such as numerous cancers and fungal infections in addition to their critical role in drug-drug interactions. Structure activity relationships (SAR), and three-dimensional quantitative structure activity relationships (3D-QSAR) represent important tools in understanding the interactions of the inhibitors with the active sites of the CYP enzymes. A comprehensive account of the QSAR studies on the major human CYPs 1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and a few other CYPs are detailed in this review which will provide us with an insight into the individual/common characteristics of the active sites of these enzymes and the enzyme-inhibitor interactions. [ABSTRACT FROM AUTHOR]

Cytochrome P450 enzymes (CYPs) are important phase I enzymes involved in the metabolism of endogenous and xenobiotic compounds mainly through mono-oxygenation reactions into more polar and easier to excrete species. In addition to their role in detoxification, they play important roles in the biosynthesis of endogenous compounds and the bioactivation of xenobiotics. Coumarins, phytochemicals abundant in food and commonly used in fragrances and cosmetics, have been shown to interact with P450 enzymes as substrates and/or inhibitors. In this review, these interactions and their significance in pharmacology and toxicology are discussed in detail. [ABSTRACT FROM AUTHOR]

The physiological role of the aryl hydrocarbon receptor (AhR), a member of the basic helix–loop–helix PER-ARNT-SIM (PAS) transcription factor family is not known. We have suggested that the AhR is involved in light signaling through binding of photoproducts with high AhR affinity. This suggestion is based on (i) the high AhR affinity of the tryptophan photoproduct formylindolo[3,2-b]carbazole (FICZ), (ii) the induction of rapid and transient expression of AhR-regulated genes by FICZ and by extracts of UV-irradiated tryptophan as well as (iii) the fact that light induces the AhR-regulated cytochrome P450s CYP1A1, CYP1B1 and CYP2S1. The transient mRNA expression caused by light and tryptophan photoproducts suggests that the biotransformation enzymes induced by AhR activation take part in a metabolic degradation of the natural AhR ligand. This study aimed at identifying the involvement of phase I and phase II enzymes in the metabolic degradation of FICZ. A cytochrome P450-dependent metabolism of FICZ giving rise to preferentially mono- and di-hydroxylated derivatives has earlier been reported. In the present study, rat and human hepatic S9 mixes were employed together with specific enzyme inhibitors and cofactors. Compared to the Aroclor-induced rat liver S9, the non-induced rat liver S9 and the human liver S9 caused a more complex metabolite profile of FICZ. The CYP1A1 enzyme was confirmed to be the most important enzyme for the first step in the metabolism. CYP1A2 was found to have overlapping specificity with CYP1A1 being able to form the same major metabolites although with different kinetics. CYP1B1 turned out to be preferentially involved in the further metabolism of dihydroxylated metabolites. Microsomal epoxide hydrolase, and as yet not identified forms of sulphotransferases and glucuronosyltransferases were also found to take part in the metabolic degradation of FICZ. Thus, tryptophan photoproducts fit into a model in which the ligand-activated AhR signaling is autoregulated by the induced metabolic enzymes. [Copyright &y& Elsevier]

Lysine deacetylases (KDACs or HDACs) are metal-dependent enzymes that regulate lysine acetylation, a post-translational modification that is present on thousands of human proteins, essential for many cellular processes, and often misregulated in diseases. The selective inhibition of KDACs would allow for understanding of the biological roles of individual KDACs and therapeutic targeting of individual enzymes. Recent studies have suggested that purportedly specific KDAC inhibitors have significant off-target binding, but the biological consequences of off-target binding were not evaluated. We compared the effects of treatment with two of the reportedly most KDAC-selective inhibitors, Tubastatin A and PCI-34051, in HT1080 cells in which the endogenous KDAC6 or KDAC8 gene has been mutated to inactivate enzyme catalysis while retaining enzyme expression. Genetic inactivation results in much stronger deacetylation defects on known targets compared to inhibitor treatment. Gene expression analysis revealed that both inhibitors have extensive and extensively overlapping off-target effects in cells, even at low inhibitor doses. Furthermore, Tubastatin A treatment led to increased histone acetylation, while inactivation of KDAC6 or KDAC8 did not. Genetic inactivation of KDAC6, but not KDAC8, impaired tumor formation in a xenograft model system, in contrast to previous reports with KDAC inhibitors suggesting the reverse. We conclude that the majority of observed biological effects of treatment with KDAC inhibitors are due to off-target effects rather than the intended KDAC inhibition. Developing a truly specific KDAC6 inhibitor could be a promising therapeutic avenue, but it is imperative to develop new inhibitors that selectively mimic genetic inactivation of individual KDACs., (© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Historically Black Colleges and Universities (HBCUs), such as Xavier University of Louisiana (Xavier), have strong cultures of mentoring underrepresented students. We report on the design and implementation of the Preparing Mentors and Advisors at Xavier (P-MAX) Program, a mentor-training program at an HBCU. Over half of the full-time Xavier faculty members have participated in at least one P-MAX event over the life of the Program, with about 60% completing the 8-hour foundational workshop. Pre/post program self-assessments indicate that mentors report significant increases in both their mentoring skills and confidence. Recommendations to consider when designing and implementing a mentor training program are provided. These range from being thoughtful about who delivers the mentoring lessons to paying close attention to the specific audience and institutional culture.

Ethyl 2-[(2-oxo-2 H -chromen-6-yl)-oxy]acetate, C 13 H 12 O 5 , a member of the pharmacologically important class of coumarins, crystallizes in the monoclinic C 2/ c space group in the form of sheets, within which mol-ecules are related by inversion centers and 2 1 axes. Multiple C-H⋯O weak hydrogen-bonding inter-actions reinforce this pattern. The planes of these sheets are oriented in the approximate direction of the ac face diagonal. Inter-sheet inter-actions are a combination of coumarin system π-π stacking and additional C-H⋯O weak hydrogen bonds between ethyl acet-oxy groups., (© Goyal et al. 2024.)

Non-small cell lung cancer (NSCLC) constitutes the predominant form of lung cancer and stands as the leading cause of cancer-related mortality in the United States. Conventional chemotherapy and radiotherapy yield suboptimal responses in a significant portion of lung cancer patients, resulting in a discouraging 5-year survival rate of approximately 15%. Despite advancements in targeted therapy and immunotherapy, many NSCLC patients exhibit either negligible or partial responses, emphasizing the pressing necessity for the discovery of innovative anti-cancer agents. Our previous study demonstrated that ABC294640, an inhibitor of one of the key enzymes in sphingolipid metabolism, sphingosine kinase 2 (SphK2), displayed anti-NSCLC activities in vitro and in vivo . In the current study, through the screening of a series of newly synthesized ceramide analogs, we have identified new compounds, particularly analogs 403 and 953, that exhibit potent anti-NSCLC activities. These compounds induce significant NSCLC apoptosis by elevating intracellular pre-apoptotic ceramide and dihydro(dh)-ceramide production. Lipidomics analyses further elucidate the alterations in ceramide and dh-ceramide species signature/proportion across different NSCLC cell-lines induced by these novel ceramide analogs. Treatments with ceramide analogs 403 and 953 remarkably inhibit NSCLC progression in vivo without observable toxicity. Collectively, these findings establish a foundation for the development of promising sphingolipid-based therapies aimed at enhancing the prognosis of NSCLC., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Many current anti-cancer drugs used to treat breast cancer mediate tumor cell death through the induction of apoptosis. Cancer cells, however, often acquire multidrug-resistance following prolonged exposure to chemotherapeutics. Consequently, molecular pathways involved in tumor cell proliferation have become potential targets for pharmacological intervention. Ceramides are tumor suppressor lipids naturally found in the cell membrane, and are central molecules in the sphingolipid signalling pathway., Methods: Our lab has targeted the ceramide signaling pathway for potential pharmacological intervention in the treatment of breast cancer. Previously, we have shown that certain ceramide analogs have therapeutic potential in the treatment of chemo-sensitive and multidrug-resistant breast cancers. Using the most active analog from our previous studies as the lead compound, new analogs containing a flavone moiety were designed and synthesized. In general, flavone derivatives often show interesting pharmacological properties, and compounds based on these molecules have been found useful in many different therapeutic areas including anti-tumor, anti-coagulants, and anti-HIV therapy., Results: Synthesis and biological evaluation of five new flavonoid ceramide analogs are reported here. These compounds were also shown to be self-fluorescent, which can be useful when investigating their distribution and action in cancer cells., Conclusion: Four out of the five flavone ceramide analogs in this study showed significant anti-proliferation activities in the three cell lines studied, MDA-MB-232, MCF-7, and MCF-7TN-R; some showing varying degrees of selectivity. The mechanisms involved in cell proliferation inhibition are complicated and further studies are needed.

The true pillar of quality higher education is well-trained, effective, and knowledgeable faculty who are invested in the success of their students. The discipline-specific knowledge required for entering an academic career as a STEM faculty member is mostly gained through academic graduate and post-doctoral training. However, formal preparation in the areas of teaching and mentoring are often lacking, and typically occur through observation of more senior colleagues. In reality, when it comes to teaching and mentoring, many STEM faculty members "build the plane while flying it," and mainly learn by trial and error. As all interactions between faculty and students can seriously impact student retention and success, there is a great need for faculty development opportunities in these areas. The focus of this communication is on the impact of mentor and pedagogical training at Xavier University of Louisiana from the STEM faculty perspective.

Aim: In this study, our goal was to study the inhibition of nicotine metabolism by P450 2A6, as a means for reduction in tobacco use and consequently the prevention of smoking-related cancers. Nicotine, a phytochemical, is an addictive stimulant, responsible for the tobacco-dependence in smokers. Many of the other phytochemicals in tobacco, including polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines, are potent systemic carcinogens. Tobacco smoking causes about one of every five deaths in the United States annually. Nicotine plasma concentration is maintained by the smokers' smoking behavior within a small range. Nicotine is metabolized by cytochrome P450s 2A6 and 2A13 to cotinine. This metabolism causes a decrease in nicotine plasma levels, which in turn leads to increased tobacco smoking, and increased exposure to the tobacco carcinogens., Methods: Using the phytochemical nicotine as a lead structure, and taking its interactions with the P450 2A6 binding pocket into consideration, new pyridine derivatives were designed and synthesized as potential selective mechanism-based inhibitors for this enzyme., Results: The design and synthesis of two series of novel pyridine-based compounds, with varying substituents and substitution locations on the pyridine ring, as well as their inhibitory activities on cytochrome P450 2A6 and their interactions with its active site are discussed here. Substitutions at position 3 of the pyridine ring with an imidazole or propargyl ether containing group showed the most optimal interactions with the P4502A6 active site., Conclusion: The pyridine compounds with an imidazole or propargyl ether containing substituent on position 3 were found to be promising lead compounds for further development. Hydrogen-bonding interactions were determined to be crucial for effective binding of these molecules within the P450 2A6 active site., Competing Interests: Conflict of interest All authors declared that there are no conflicts of interest.

Diversity of backgrounds and life experiences on scientific teams is known to lead to more innovative ideas and better scientific products. However, in the United States, the percentages of individuals from underrepresented racial and ethnic groups who obtain doctoral degrees in the Sciences continue to be significantly lower than their percentages in the population. This has resulted in the need for nation-wide initiatives to remedy this inequality, and consequently produce more productive teams of scientific minds. Xavier University of Louisiana is a historically Black and Catholic university that is widely recognized in the US for the success of its undergraduate Science, Technology, Engineering, and Mathematics (STEM) programs. Project Pathways at Xavier is one of ten federally-funded Building Infrastructure Leading to Diversity (BUILD) programs with the overarching goal of diversifying the Biomedical research workforce. Project Pathways is designed as a holistic, integrated, and coordinated program across Biomedical academic departments, student academic and career support offices, and the University's faculty development center. The overall hypothesis of Project Pathways is that if individuals from groups underrepresented in scientific research careers are provided with a) early awareness and deepening exposure to Biomedical careers, b) supportive relationships as they move through the pathway, c) suitable infrastructure, and d) meaningful engagement in Biomedical research experiences and adequate research resources, then a higher number will succeed in entering and successfully completing graduate programs, leading to increased diversity in the Biomedical research workforce. Here, the significant strides of this program during its first five-year funding cycle are presented.

Xavier University of Louisiana has a national reputation for producing science, technology, engineering, and mathematics (STEM) graduates who go on to obtain MD and PhD degrees. According to a 2013 National Science Foundation report, Xavier is ranked first in producing African American graduates who go on to receive life sciences PhD degrees, fifth in the nation in producing African American graduates who go on to receive science and engineering PhD degrees, and seventh in producing African American graduates who go on to receive physical sciences PhD degrees. Xavier is currently third among the nation's colleges and universities in the number of African American graduates enrolled in medical school, according to data compiled by the Association of American Medical Colleges, and ranked first in the number of African American alumni who successfully complete their medical degrees. The success of Xavier's graduates is due to a combination of university-based student support initiatives and externally funded programs, in particular, the Building Infrastructure Leading to Diversity (BUILD), Maximizing Access to Biomedical Research Careers (MARC) U*STAR, and Research Initiative in Scientific Enhancement (RISE) programs. These three programs, funded by the Training, Workforce Development, and Diversity (TWD) Division at the National Institutes of Health (NIH), offer select trainees undergraduate research opportunities, support mechanisms, and a variety of activities designed to improve their potential for success in graduate school. The BUILD, MARC U*STAR, and RISE programs work closely together and with the University to leverage the resources provided by each in order to provide the best experience possible for their students with a minimum of redundancy of effort. This chapter focuses on the program components and how the programs work together.

Cytochrome P450 enzymes are a superfamily of hemoproteins involved in the metabolism and detoxification of endogenous and exogenous compounds. P450s are involved in the bioactivation of certain procarcinogens leading to the production of carcinogenic species. This has resulted in P450s' popularity as targets in cancer research. Developing selective and potent mechanism-based inhibitors for these enzymes is expected to be the key to understanding their mechanisms of action, as well as, developing potential anticancer agents. Our group has shown that certain aryl and aryl-alkyl acetylenes act as inhibitors of these enzymes. In an attempt to increase the number of selective P450 inhibitors available for enzymatic studies, five novel dibenzofuran ethers and esters have been designed and synthesized successfully.

The title compound, C 17 H 18 O 2 , crystallizes in two-dimensional sheets, in which the 2-(pentyloxy)dibenzo[ b , d ]furan molecules are arranged in a head-to-head and tail-to-tail fashion that enables hydrophobic interactions between fully extended 2-pentoxy chains and π-π stacking between dibenzofuran rings in adjacent rings. Nearest intermolecular π-π stacking contacts are 3.3731 (12) Å. The molecule is nearly planar with an r.m.s. deviation of 0.0803 Å from the mean plane defined by the nineteen non-hydrogen atoms.

In the title flavonoid derivative, C 19 H 16 O 5 , the chromene portion is planar (r.m.s. deviation = 0.022 Å) with the substituents lying closely to the same plane. The dihedral angle between its mean plane and that of the benzene ring is 4.9 (1)°. This planarity is due, in part, to the presence of a strong intramolecular C-H⋯O hydrogen bond and to two weak C-H⋯O contacts. In the crystal, neighboring molecules are linked by a C-H⋯O hydrogen bond and a C-H⋯ π interaction, forming chains along the a -axis direction.

Non-small cell lung cancer (NSCLC) accounts for about 85-90% of lung cancer cases, and is the number one killer among cancers in the United States. The majorities of lung cancer patients do not respond well to conventional chemo- and/or radio-therapeutic regimens, and have a dismal 5-year survival rate of ∼15%. The recent introduction of targeted therapy and immunotherapy gives new hopes to NSCLC patients, but even with these agents, not all patients respond, and responses are rarely complete. Thus, there is still an urgent need to identify new therapeutic targets in NSCLC and develop novel anti-cancer agents. Sphingosine kinase 2 (SphK2) is one of the key enzymes in sphingolipid metabolism. SphK2 expression predicts poor survival in NSCLC patients, and is associated with Gefitinib-resistance. In this study, the anti-NSCLC activities of ABC294640, the only first-in-class orally available inhibitor of SphK2, were explored. The results obtained indicate that ABC294640 treatment causes significant NSCLC cell apoptosis, cell cycle arrest and suppression of tumor growth in vitro and in vivo. Moreover, lipidomics analyses revealed the complete signature of ceramide and dihydro(dh)-ceramide species in the NSCLC cell-lines with or without ABC294640 treatment. These findings indicate that sphingolipid metabolism targeted therapy may be developed as a promising strategy against NSCLC., (© 2017 UICC.)