Eight new beta-N-substituted acyl hydrazides along with their corresponding acyl derivatives were synthesized and screened for in vitro beta-glucuronidase inhibition and found to be active against the enzyme. All of these compounds were found to be noncompetitive inhibitors except for N'-(2-cyanoethyl)-4-hydroxy benzohydrazide (10), which was found to be an uncompetitive inhibitor. Structure-activity relationship studies indicated that the benzyloxy group present in compounds 12 and 13 is responsible for the beta-glucuronidase inhibition activity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1248/cpb.50.1443 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeted inhibition of Gus-expressing to promote intestinal stem cell and epithelial renovation contributes to the relief of irinotecan chemotoxicity by dehydrodiisoeugenol.
Acta Pharm Sin B
December 2024
The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to -glucuronidase (Gus) converting 10--glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing.
View Article and Find Full Text PDFHeparanase 2 Modulation Inhibits HSV-2 Replication by Regulating Heparan Sulfate.
Viruses
November 2024
Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
The host enzyme heparanase (HPSE) facilitates the release of herpes simplex virus type 2 (HSV-2) from target cells by cleaving the viral attachment receptor heparan sulfate (HS) from infected cell surfaces. HPSE 2, an isoform of HPSE, binds to but does not possess the enzymatic activity needed to cleave cell surface HS. Our study demonstrates that HSV-2 infection significantly elevates HPSE 2 protein levels, impacting two distinct stages of viral replication.
View Article and Find Full Text PDFSteroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation.
Biomolecules
November 2024
Thrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, Israel.
Bone metastasis and steroids are known to activate the coagulation system and induce osteoporosis, pathological bone fractures, and bone pain. Heparanase is a protein known to enhance the hemostatic system and to promote angiogenesis, metastasis, and inflammation. The objective of the present study was to evaluate the effects of steroids and malignancy on the coagulation factors and osteoblast activity in the bone tissue.
View Article and Find Full Text PDF5-Aminolevulinic acid improves strawberry salt tolerance through a NO-HO signaling circuit regulated by FaWRKY70 and FaWRKY40.
J Adv Res
December 2024
College of Horticulture, Nanjing Agricultural University, Nanjing 21095, China. Electronic address:
Introduction: 5-Aminolevulinic acid (ALA) is an essential biosynthetic precursor of tetrapyrrole compounds, naturally occurring in all living organisms. It has also been suggested as a new plant growth regulator. Treatment with ALA promotes strawberry Na homeostasis under salt stress.
View Article and Find Full Text PDFSynthetic glycol-split heparin tri- and tetrasaccharides provide new insights into structural peculiarities for antiheparanase activity.
Bioorg Med Chem
December 2024
Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, via G. Colombo 81, 20133 Milano, Italy.
Article Synopsis
- Heparanase is a key enzyme in the breakdown of heparan sulfate, contributing to tumor growth and metastasis, making it a target for cancer treatments.
- Researchers synthesized specific trisaccharides and a tetrasaccharide that inhibit heparanase activity, focusing on glycol-split versions as potential inhibitors.
- Studies using STD NMR and molecular docking revealed that these glycol-split trisaccharides had stronger binding and inhibitory effects against heparanase compared to their intact forms, providing insight into their mechanisms.
Want 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!