Heterocyclic Compounds Commons^™

Design And In Silico Modeling Of Heterocyclic-Based Xanthone Derivatives As Potential Anticancer Agents Through Tyrosine Kinase Inhibition, Yehezkiel Steven Kurniawan, Ervan Yudha, Nela Fatmasari, Radite Yogaswara, Harno Dwi Pranowo, Eti Nurwening Sholikhah, Jumina Jumina

Makara Journal of Science

Cancer is one of the deadliest diseases nowadays, and tyrosine kinase receptors play crucial roles in cancer cell survival, differentiation, proliferation, and migration. This study designed and developed a new inhibitor from heterocyclic-based xanthone derivatives to target two tyrosine kinase receptors, epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR), through in silico screening. Eighteen heterocyclic-based xanthones were evaluated through molecular docking for both receptors. All heterocyclic-based xanthones gave the root mean square deviation (RMSD) value lower than 2.00 Å. Xanthone with isobenzothiazole substituent (iBzThio) was found as the most potent inhibitor with binding energies of -10.60 and …

Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves

Honors Undergraduate Theses

The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By …

Colorectal Cancer: Differential Gene Expression And In Vitro Response To 5-Fluorouracil, Novel Fluoropyrimidine F10, And Potential Synergy With Lupeol, Shrey D. Thaker, Jenny Paredes, Jone Garai, Laura A. Martello, William H. Gmeiner, Jovanny Zabaleta, Jennie Williams

School of Medicine Faculty Publications

Colorectal cancer (CRC) remains one of the most lethal malignancies in the United States, with African American (AA) patients experiencing disproportionately higher incidence and mortality compared to Caucasian Americans (CAs). These disparities have been linked to tumor-intrinsic genomic differences, including microsatellite instability (MSI) and p53 mutation status, which may influence chemotherapeutic response, particularly to the standard-of-care agent 5-fluorouracil (5-FU). However, mechanistic insights have been limited by the lack of racially diverse preclinical models. Here, we evaluated the efficacy of F10 (a novel fluoropyrimidine polymer) vs. 5-FU using AA- and CA-derived CRC cell lines with distinct MSI and p53 profiles. MTT …

In Situ-Generated Volumetric Dried Plasma Spots For The Analysis Of Edaravone And Metabolites In Animal Models, Michele Protti, Roberta Di Lecce, Jiri Adamec, Luca G. Regazzoni, Valeria Valsecchi, Claudia Volpi, Roberto Mandrioli, Laura Mercolini

School of Graduate Studies Faculty Publications

In this study, for the first time rat plasma microsampling was carried out by means of in situ-generated volumetric dried plasma spot (vDPS) technology and applied to the determination of the neuroprotective agent edaravone and its sulphate and glucuronide metabolites. Sampling was performed using Telimmune® plasma separation cards (vPSC), which allow the formation of volumetrically accurate dried plasma spots (3 µL) from blood drops deposited on them. After accelerated forced drying and solvent extraction in methanol, drying and redissolution, analytes were baseline separated and quantified through an original HPLC-MS/MS analytical method. Validation assays provided excellent results, with detection limits between …

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

Hydralazine Inhibits Cysteamine Dioxygenase To Treat Preeclampsia And Senesce Glioblastoma, Kyosuke Shishikura, Jiasong Li, Yiming Chen, Nate R. Mcknight, Thomas P. Keeley, Katelyn A. Bustin, Eric W. Barr, Snehil R. Chilkamari, Mahaa Ayub, Sun Woo Kim, Zongtao Lin, Ren-Ming Hu, Kelly Hicks, Xie Wang, Donald M. O'Rourke, J. Martin Bollinger, Zev A. Binder, William H. Parsons, Kirill A. Martemyanov, Aimin Liu, Megan L. Matthews

SKMC Student Presentations and Publications

Hydralazine (HYZ), a treatment for preeclampsia and hypertensive crisis, is listed by the World Health Organization as an essential medicine. Its mode of action has remained unknown through its seven decades of clinical use. Here, we identify 2-aminoethanethiol dioxygenase (ADO), a key mediator of targeted protein degradation, as a selective HYZ target. The drug chelates ADO's metallocofactor and can alkylate one of its ligands. The resultant inactivation stabilizes regulators of G protein signaling (RGS4 and RGS5) that ADO normally marks for proteolysis, explaining the drug's vasodilatory activity and comporting with observations of diminished RGS levels in both clinical preeclampsia and …

Ketorolac Use Following Operative Clavicle Fracture Fixation Is Not Associated With Increased Nonunion Or Surgical Complications: A Propensity-Matched Analysis, Tuckerman Jones, Tej Joshi, Akhil Katakam, Daniella Ogilvie, Sefy Paulose, Balazs Galdi

Wills Eye Hospital Papers

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, are commonly used for postoperative pain management. Concerns about their potential impact on bone healing have been raised. This study investigated the relationship between ketorolac use and postoperative complications following clavicle surgery, including nonunion rates.

METHODS: This retrospective cohort study used the TriNetX Research Database to identify patients who underwent surgical fixation of clavicle fractures between 2002 and 2022. Two propensity-matched cohorts were created: patients who received postoperative ketorolac and those who did not. Primary outcomes included nonunion diagnosis and revision surgery; secondary outcomes included opioid use, wound disruption, surgical site infection, and …

Total Synthesis Of The Marine Cytotoxic Mansouramycin And Derivatives, Aditya Dantu, Gabriella L. Madrigal, Neel Gondi, David Osazee, Ahmad Amro, Whard Alsabbagh, Shizue Mito

Research Colloquium

Purpose: Isoquinolinequinones are a group of organic compounds which are composed of an isoquinoline fused to a quinone ring. This class of molecules is known to exhibit a wide variety of biological activities, including cytotoxic and antitumor properties. Among the many families of isoquinolinequinones are the Caulibugulones and Mansouramycins, which exhibit anticancer properties and are thus desirable subjects for cancer-related research. They are obtained by isolation from marine bryozoan Caulibugula intermis and marine Streptomyces sp respectively, however these compounds are difficult to extract. Thus, organic synthesis is being explored as a method of obtaining them; this project focuses on the …

Advances In Indole Chemistry: Regiodivergent Annulations And Bridged Azacycle Synthesis, Zachary Tihomir Protich

Dartmouth College Ph.D Dissertations

An important aspect for the research and development of new drug therapies is the ability to use modular synthetic methods to rapidly access structurally diverse drug-like building blocks. Nitrogen-containing heterocycles represent one of the most prevalent structural motifs found in pharmaceutical agents and biologically active natural products. However, despite their ubiquity, existing methods for accessing these structures often remain limited in scope, efficiency, and structural diversity, particularly when targeting densely functionalized or sterically demanding scaffolds from simple starting materials.

To address this problem, the research described in this dissertation focuses on the design and development of (3+2) annulation reactions for …

Unplanned Hospitalization Among Advanced Prostate Cancer Patients By Diabetes Status: A Population-Based Study, Amy L. Shaver, Krupa Gandhi, Scott W. Keith, Nikita Nikita, Christopher C. Yang, Felix J. Kim, Hushan Yang, William K. Kelly, Stephen J. Freedland, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

BACKGROUND: Older adults with advanced prostate cancer and type 2 diabetes mellitus are underrepresented in trials of androgen receptor pathway inhibitors. This study examined changes in unplanned hospitalization rates in patients receiving androgen receptor pathway inhibitors by type 2 diabetes mellitus status and assessed if unplanned hospitalization varies according to androgen receptor pathway inhibitors.

METHODS: This population-based study of advanced prostate cancer patients aged older than 66 years used Surveillance, Epidemiology, and End Results-Medicare data. Prepost androgen receptor pathway inhibitor initiation changes and androgen receptor pathway inhibitor differences in unplanned hospitalization rates were estimated by adjusted incidence rate ratio with …

Synergistic Cefiderocol-Containing Antibiotic Combinations Active Against Highly Drug-Resistant Acinetobacter Baumannii Patient Isolates With Diverse Resistance Mechanisms, Justin Halim, Andrew P. Keane, Jeannete Bouzo, Tope Aderibigbe, Jessica A. Chicola, Katie T. Nolan, Keertana Jonnalagadda, Jason X. Tran, Valerie J. Carabetta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Acinetobacter baumannii is a nosocomial pathogen known for rapidly developing resistance to nearly all antibiotics, including last-line agents. Cefiderocol, a novel siderophore cephalosporin, has shown in vitro activity against A. baumannii and is now used clinically, but resistance is emerging. Data on cefiderocol-based antibiotic combinations are limited.

OBJECTIVES: To evaluate the in vitro activity of cefiderocol alone and in combination with other antibiotics against XDR and PDR A. baumannii clinical isolates, and to explore resistance mechanisms underlying cefiderocol synergy.

METHODS: We tested 21 XDR/PDR clinical isolates and one NDM-1-producing strain using broth microdilution and checkerboard assays with cefiderocol and …

Novel Piperidone And Bispidine Derivatives: A New Approach In Cancer Therapy, Lereen Khaled Youssry

Theses and Dissertations

Cancer remains the second leading cause of death worldwide. As a result, scientists have been trying to find novel therapeutic approaches that target specific metabolic pathways selective to tumor cells. In this study, two novel piperidone and bispidine derivatives, organic molecules that target polyamine metabolism, were synthesized, and their potential cytotoxic, antioxidant and anti-inflammatory effects were investigated. Polyamines are naturally occurring metabolites that were reported to be in excess at cancer cells and were accounted for tumor proliferation, invasion and metastasis. Accordingly, the novel piperidone and bispidine derivatives were expected to disrupt tumor growth and progression via up-regulation of key …

Brivaracetam For Spinal Cord Injury-Related Neuropathic Pain: Results Of A Pilot Double-Blinded, Randomized, Placebo-Controlled Clinical Trial, Leslie R. Morse, Ricardo A. Battaglino, Nguyen Nguyen, Brian Devries, Abigail Welch, Ana Lucia Battaglino, Clas Linnman, Michael Stillman, Robert Wudlick, Joda Glossner, Grant Anderton, Richard Goldstein, Scott P. Falci

Department of Medicine Faculty Papers

OBJECTIVE: Assess feasibility, safety, and tolerability of 3 months of oral brivaracetam for severe (9-10/10) spinal cord injury-related neuropathic pain.

METHODS: We conducted a multisite pilot study where adults were randomized to 3 months of brivaracetam (100 mg BID) or placebo. Pain was assessed via the Brief Pain Inventory, the International Spinal Cord Injury Pain Basic Dataset (version 2.0), and a daily pain diary.

RESULTS: We enrolled 24 participants across 2 sites and 14 participants were included in the final analysis (n = 8 placebo, n = 6 brivaracetam). The drug was tolerated with expected, nonserious side effects (nausea if …

Cobenfy(Xanomeline/Trospium) Vs. Clozapine For Treatment-Resistant Schizophrenia, Harmann Singh, Akash M. Patel, Abdullah Noory, Kush C. Patel, Simran Gandhi

Rowan-Virtua Research Day

Background: Treatment-resistant schizophrenia (TRS) poses significant therapeutic challenges. Although clozapine remains the gold-standard pharmacologic treatment for TRS, its clinical utility is hampered by severe side effects and intensive monitoring requirements. KarXT (Cobenfy), a combination of xanomeline and trospium chloride, represents a novel antipsychotic approach by targeting muscarinic M1/M4 receptors instead of dopamine D2 pathways.

Hypothesis: KarXT offers comparable efficacy to clozapine with a more favorable safety and tolerability profile, making it a viable alternative for patients with TRS.

Methods: A systematic review was conducted to identify studies from 2015–2025 evaluating KarXT in schizophrenia. Sources included PubMed, ClinicalTrials.gov, FDA databases, ICER …

Hydralazine-Induced Vasculitis Resulting In Large Pleural Effusion And Progressive Renal Dysfunction, Michael A. Acevedo, Hammad Choudhry

Rowan-Virtua Research Day

Hydralazine is a vasodilator commonly used to treat high blood pressure. Even with the safety profile of Hydralazine, it is necessary to know that it may lead to Hydralazine-Induced Vasculitis. Here, we discuss how this rare side effect can present in an 80-year-old female with a past medical history of hypertension who presented to the emergency department with complaints of progressive shortness of breath on exertion and while lying supine. Further evaluation revealed a large right-sided pleural effusion with consolidation at the right lower lobe. The patient’s dyspnea worsened, and the surgical team placed a chest tube. The patient also …

Identifying Early Presentation Of Serotonin Syndrome In A 20-Year-Old Male Prescribed Clomipramine And Quetiapine: A Case Report, Veronica Alday, Justin Scarano, Jonathan Yuh, Christie Richardson

Rowan-Virtua Research Day

Serotonin syndrome, a potentially life-threatening condition, can be challenging to diagnose due to its diverse etiology and varied symptomatology. Despite its severity, serotonin syndrome may present from mild to fatal, with symptoms such as autonomic instability, altered mental status, and neuromuscular excitation (e.g. muscle rigidity, hyperreflexia). Here, we present a 20-year-old male with an extensive psychiatric history who was prescribed clomipramine and developed serotonin syndrome. Few cases of serotonin syndrome have been reported to date, exacerbating the difficulty in recognizing and quickly treating such cases. Cases of serotonin syndrome should continue to be reported, in order to familiarize clinicians with …

Dabigatran Reduced Acute Microgliosis In A Mouse Model With Tbi, Nicholas R. Eltman, Rashmeena Abbasi, Mary C. Kosciuk, Syed Ahmed, Jose L. Pascual, Randel L. Swanson, Nimish K. Acharya

Rowan-Virtua Research Day

Objective:

The study objective was to investigate the acute anti-inflammatory effects of dabigatran in a preclinical mouse controlled cortical impact (CCI) model of severe traumatic brain injury (TBI).

Design

Mice were separated into three groups: controlled cortical impact (CCI) with dabigatran (drug treatment, n=5), CCI with saline (positive control, n=5), and sham CCI without saline or dabigatran (negative control, n=3). Dabigatran (80mg/kg) or saline was administered orally at 2, 10, 18, 26, 34, and 42 hours following experimental CCI in the drug treatment or positive control groups, respectively. Animals in the negative control group received sham CCI only. 48h following …

Literature Review: Prazosin Used For Ptsd In Pregnancy, Afshan Khan, Natali Sharma, Rebekah M. Dietrich, Martin Forsberg

Rowan-Virtua Research Day

Posttraumatic Stress Disorder (PTSD) affects 3–4% of pregnant and postpartum individuals and is associated with complications such as preterm birth, low birth weight, and postpartum depression. Pharmacologic treatment options during pregnancy are limited by concerns about fetal safety.

Methods: A literature review was conducted focusing on studies reporting maternal or neonatal outcomes following prazosin exposure in pregnancy.

Results: One observational study of 11 pregnancies found 54.5% had uneventful outcomes, with rates of preterm birth, miscarriage, and preeclampsia similar to the general population. Hypotension and limited lactation data remain concerns.

Conclusion: Early evidence suggests prazosin may be a relatively safe and …

Examining The Relationship Between Sleep Habits And Caffeine Consumption, Daniel Calaff, Rachel Pruchno

Rowan-Virtua Research Day

Sleep is essential for cognitive function, mood regulation, immune defense, and metabolic health. Despite widespread caffeine use, its impact on sleep remains debated. It was initially hypothesized that higher caffeine consumption would correlate with greater sleep disturbances. This study explored the relationship between caffeine consumption and sleep habits in a general adult population using a Qualtrics-based self-report survey. Participants (n=93) reported average hours slept per night, time to fall asleep, and number of nighttime awakenings. Caffeine consumption was calculated based on reported intake and categorized into four dosage groups. Sleep outcomes were statistically compared using ANOVA, t-tests, and Pearson correlation. …

Mechanisms Mediating The Protective Effects Of Caffeine On Alzheimer’S Disease Progression, Jessica Ivanov, Malky Bernat, Joshua Drawbaugh, Jeremy Mehta, Namira Rahmani, Saikumar Thellapally

Rowan-Virtua Research Day

Background: This review aims to examine the molecular mechanisms through which caffeine may exert neuroprotective effects against Alzheimer’s Disease (AD).

Methods: A literature review was done across PubMed and Embase to identify studies between 2000 and 2024, exploring the mechanism behind caffeine’s effects on AD. The criteria focused on peer-reviewed articles involving human or animal models. Information was gathered on study design, participant characteristics, caffeine consumption, proposed mechanisms, and effects on cognition.

Results: The studies support caffeine's potential as a therapeutic, neuromodulator against AD through six mechanisms: inhibition of adenosine A2A receptors, decreased amyloid-beta production and aggregation, promotion of amyloid …