Hybrids of Benzenesulfonamide Oxadiazole Derivatives with Dual CA II and COX-2 Inhibitory Activity Demonstrating Antiglaucoma and Anti-inflammatory Action: Synthesis, In Silico Insights, and In Vitro and In Vivo Bioevaluation

High Resolution Image Download MS PowerPoint Slide In this study, new sulfonamide derivatives 5a–g and 10a–e were designed, synthesized, and biologically evaluated for their anti-inflammatory activity. In vitro COX inhibitory assays were performed, and among the synthesized compounds, 5b and 5d emerged as the most promising leads, combining COX-2 inhibition with remarkable selectivity (COX-2 IC 50 = 0.13 and 0.05 μM, SI = 9.25 and 12.02, respectively) and h CA II inhibition ( K i = 39.1 nM and 62.6 nM, respectively) with a high selectivity index over h CA I (SI = 933.8 and 704.2, respectively). In vivo evaluations confirmed that compounds 5b and 5d (50 mg/kg) possess promising analgesic and anti-inflammatory effects, with rapid onset, sustained duration of action, and a reduced ulcerogenic liability, indicating an improved gastrointestinal safety profile. Additionally, 5b showed significant and sustained IOP-lowering effects in antiglaucoma animal models. Computational studies and X-ray crystallography were performed as a proof of concept.

Authors

Institutions

Publication Details

Journal
Journal of Medicinal Chemistry
Published
2026-07-01
DOI
https://doi.org/10.1021/acs.jmedchem.6c01117
Primary Topic
Enzyme function and inhibition
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Hybrids of Benzenesulfonamide Oxadiazole Derivatives with Dual CA II and COX-2 Inhibitory Activity Demonstrating Antiglaucoma and Anti-inflammatory Action: Synthesis, In Silico Insights, and In Vitro and In Vivo Bioevaluation

Alessandro Bonardi, Ahmed A. Attia, Marta Ferraroni, Husam Nassar et al.
Journal of Medicinal Chemistry
Enzyme function and inhibition
article

Hybrids of Benzenesulfonamide Oxadiazole Derivatives with Dual CA II and COX-2 Inhibitory Activity Demonstrating Antiglaucoma and Anti-inflammatory Action: Synthesis, In Silico Insights, and In Vitro and In Vivo Bioevaluation

Alessandro Bonardi, Ahmed A. Attia, Marta Ferraroni, Husam Nassar, Claudiu T. Supuran, Matthias Schmidt, Manal Abdel Fattah Ezzat, Yomna Khater, Heba Abdelrasheed Allam, Emad M. Seif, Hany S. Ibrahim, Andrea Angeli, Rabab Ahmed Rasheed, Omnia A. M. Abd El-Ghafar
article en

Abstract

High Resolution Image Download MS PowerPoint Slide In this study, new sulfonamide derivatives 5a–g and 10a–e were designed, synthesized, and biologically evaluated for their anti-inflammatory activity. In vitro COX inhibitory assays were performed, and among the synthesized compounds, 5b and 5d emerged as the most promising leads, combining COX-2 inhibition with remarkable selectivity (COX-2 IC 50 = 0.13 and 0.05 μM, SI = 9.25 and 12.02, respectively) and h CA II inhibition ( K i = 39.1 nM and 62.6 nM, respectively) with a high selectivity index over h CA I (SI = 933.8 and 704.2, respectively). In vivo evaluations confirmed that compounds 5b and 5d (50 mg/kg) possess promising analgesic and anti-inflammatory effects, with rapid onset, sustained duration of action, and a reduced ulcerogenic liability, indicating an improved gastrointestinal safety profile. Additionally, 5b showed significant and sustained IOP-lowering effects in antiglaucoma animal models. Computational studies and X-ray crystallography were performed as a proof of concept.

Journal of Medicinal Chemistry
Cairo University (EG), Mansoura University (EG), Nahda University (EG), Luther University (KR), Czech Academy of Sciences, Institute of Experimental Medicine (CZ), Istituto Nazionale di Fisica Nucleare, Sezione di Firenze (IT), Medicina (PL), Cell Medica (Switzerland) (CH), Institute of Pharmacology (CZ), University of Florence (IT), Egyptian Russian University (EG), Martin Luther University Halle-Wittenberg (DE), October University of Modern Sciences and Arts (EG)
Openalex Percentile: Top 11%
Enzyme function and inhibition
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.