The syntheses of five metabolites of the antiinflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid) are described, viz. 6-hydroxyetodolac, N-methyletodolac, 4-ureidoetodolac, 8-(1'-hydroxy)etodolac, and 4-oxoetodolac. These syntheses were used to confirm the identities of the metabolites. The metabolites themselves, as well as the previously reported metabolite 7-hydroxyetodolac, were tested in a rat adjuvant edema model and in vitro for their capacity to block prostaglandin production in chondrocyte cells. All either were inactive or possessed only marginal activity. The isolation of N-methyletodolac and 4-oxoetodolac from human and rat urine, respectively, is also described.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm00117a009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.
AAPS PharmSciTech
May 2024
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
Article Synopsis
- The study developed a propellant-free topical spray formulation of Etodolac, an effective NSAID for treating pain and inflammation, which is user-friendly and environmentally sustainable.
- Different formulations were created by varying concentrations of components, and the optimized version showed significant drug content uniformity and quick evaporation time, indicating efficient application.
- The spray formulation improved skin permeability and drug deposition compared to a pure solution, showing promising results for effectiveness while ensuring safety and no skin irritation.
Modeling Path Importance for Effective Alzheimer's Disease Drug Repurposing.
Pac Symp Biocomput
January 2024
Biomedical Informatics Department, The Ohio State University, Columbus, OH 43210, USA*Co-first author; authors contributed equally to this work.
Recently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex networks that integrate multiple interaction types, such as protein-protein interactions, to more effectively identify candidate drugs. However, existing approaches typically assume paths of the same length in the network have equal importance in identifying the therapeutic effect of drugs.
View Article and Find Full Text PDFModeling Path Importance for Effective Alzheimer's Disease Drug Repurposing.
ArXiv
October 2023
Biomedical Informatics Department, The Ohio State University, Columbus, OH 43210, USA.
Recently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex networks that integrate multiple interaction types, such as protein-protein interactions, to more effectively identify candidate drugs. However, existing approaches typically assume paths of the same length in the network have equal importance in identifying the therapeutic effect of drugs.
View Article and Find Full Text PDF"Don't let it to air": A cautionary tale of the potential consequences of surgery of residual cancer.
Brain Behav Immun
July 2023
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada; Department of Biochemistry, Microbiology Immunology, University of Ottawa, Ottawa, Canada; Department of Surgery, Faculty of Medicine, University of Ottawa, Ottawa, Canada. Electronic address:
In this issue of the BBI, Haldar et al. demonstrate that major surgical stress from laparotomy caused a significant increase in post-operative metastatic burden in a mouse model of cancer. They identified this metastatic outbreak was driven by a novel mechanism of direct, surgery-induced activation of the primary tumour which, if left in situ, released pro-metastatic factors (IL-6, IL-8, and VEGF).
View Article and Find Full Text PDFPerioperative escape from dormancy of spontaneous micro-metastases: A role for malignant secretion of IL-6, IL-8, and VEGF, through adrenergic and prostaglandin signaling.
Brain Behav Immun
March 2023
School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel. Electronic address:
We recently showed that a minimally-invasive removal of MDA-MB-231 primary tumors (PTs) and elimination of their secreted factors (including IL-6, IL-8, VEGF, EGF, PDGF-aa, MIF, SerpinE1, and M-CSF), caused regression of spontaneous micro-metastases into a non-growing dormant state. To explore the underlying mechanisms and potential clinical ramifications of this phenomenon, we herein used the MDA-MB-231 human breast cancer cell-line, in-vitro, and in vivo following orthotopic implantation in immune-deficient BALB/C nu/nu mice. Employing bioluminescence imaging, we found that adding laparotomy to minimally-invasive removal of the PT caused an outbreak of micro-metastases.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!