Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti-inflammatory properties: Synthesis, biological evaluation and molecular modeling studies
| Autor: | Birsen Tozkoparan, Ayse Uzgoren-Baran, Banu Cahide Tel, Mevlüt Ertan, Deniz Sarıgöl, Gürol Okay, Oya Unsal-Tan, Keriman Ozadali-Sari, Inci Kazkayasi, Elif Inci Somuncuoglu |
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| Přispěvatelé: | Okay, Gürol |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Nociception
Naproxen medicine.drug_class Stereochemistry Clinical Biochemistry Analgesic Pharmaceutical Science Pain Molecular modeling Pharmacology Molecular Dynamics Simulation Carrageenan Biochemistry Anti-inflammatory Mice Structure-Activity Relationship Ulcerogenic risk In vivo Drug Discovery medicine Structure–activity relationship Animals Edema Humans Molecular Biology Pain Measurement Inflammation Analgesics biology Chemistry Organic Chemistry Anti-Inflammatory Agents Non-Steroidal Thiones Biological activity Triazoles Thiazolo[3 2-b]-1 2 4-triazole Molecular Docking Simulation Disease Models Animal Thiazoles Docking (molecular) Drug Design Analgesic/anti-inflammatory activity biology.protein Naproxen derivatives Molecular Medicine Cyclooxygenase medicine.drug |
| Popis: | 3-Substituted-1,2,4-triazole-5-thiones are versatile synthetic intermediates for the preparation of several biologically active N-bridged heterocyclic compounds, given that they have two reactive sites, thiocarbonyl and an amine nitrogen (N-1/N-4). For several years, our interest has focused on the synthesis of novel heterocyclic systems derived from 3-substituted-1,2,4-triazole-5-thiones having analgesic/anti-inflammatory activity. In this study, a series of novel thiazolo[3,2-b]-1,2,4-triazole-6(5H)-one derivatives bearing naproxen was synthesized and evaluated for their in vivo analgesic and anti-inflammatory properties in acute experimental pain and inflammation models. The compounds were also tested for their ulcerogenic potential. Our findings showed that all the newly synthesized derivatives attenuate nociception and inflammation compared with a control. All the synthesized compounds exhibited much lower ulcerogenic risk than the standard drugs indomethacin and naproxen. Some compounds with significant analgesic and/or anti-inflammatory activities as well as low ulcer scores were further evaluated for in vitro COX-1 and COX-2 inhibitory potential in a COX-catalyzed prostaglandin biosynthesis assay. Among the tested compounds, compound 1q showed the highest selectivity index (SI) of 4.87. The binding mode for some of the tested compounds to the cyclooxygenase (COX) enzymes was predicted using docking studies. (C) 2015 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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