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Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2019 Mar; Vol. 84, pp. 260-268. Date of Electronic Publication: 2018 Nov 22. - Publication Year :
- 2019
-
Abstract
- Trimellitimides 6-21 were prepared and investigated in vivo for anti-inflammatory and ulcerogenic effects and in vitro for cytotoxicity. They were subjected to in vitro cyclooxygenase (COX-1/2) and carbonic anhydrase inhibition protocols. Compounds 6-11 and 18 exhibited anti-inflammatory activities and had median effective doses (ED <subscript>50</subscript> ) of 34.3-49.8 mg kg <superscript>-1</superscript> and 63.6-86.6% edema inhibition relative to the reference drug celecoxib (ED <subscript>50</subscript> : 33.9 mg kg <superscript>-1</superscript> and 85.2% edema inhibition). Compounds 6-11 and 18 were weakly cytotoxic at 10 μM against 59 cell lines compared with the reference standard 5-fluorouracil (5-FU). Compounds 6-11 had optimal selectivity against COX-2. The selectivity index (SI) range was >200-490 and was comparable to that for celecoxib [COX-2 (SI) > 416.7]. In contrast, compounds 12, 13, and 16-18 were nonselective COX inhibitors with a selectivity index range of 0.92-0.25. The carbonic anhydrase inhibition assay showed that sulfonamide incorporating trimellitimides 6-11 inhibited the cytosolic isoforms hCA I and hCA II, and tumor-associated isoform hCA IX. They were relatively more susceptible to inhibition by compounds 8, 9, and 11. The K <subscript>I</subscript> ranges were 54.1-81.9 nM for hCA I, 25.9-55.1 nM for hCA II, and 46.0-348.3 nM for hCA IX. © 2018 Elsevier Science. All rights reserved.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Anti-Ulcer Agents chemical synthesis
Anti-Ulcer Agents chemistry
Anti-Ulcer Agents therapeutic use
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Carbonic Anhydrase Inhibitors pharmacology
Carbonic Anhydrase Inhibitors therapeutic use
Carbonic Anhydrases chemistry
Carbonic Anhydrases metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Cyclooxygenase 1 chemistry
Cyclooxygenase 1 metabolism
Cyclooxygenase 2 chemistry
Cyclooxygenase 2 metabolism
Cyclooxygenase Inhibitors pharmacology
Cyclooxygenase Inhibitors therapeutic use
Drug Design
Edema chemically induced
Edema drug therapy
Edema pathology
Edema veterinary
Humans
Imides pharmacology
Imides therapeutic use
Mice
Rats
Structure-Activity Relationship
Sulfonamides pharmacology
Sulfonamides therapeutic use
Ulcer drug therapy
Ulcer pathology
Anti-Inflammatory Agents chemical synthesis
Carbonic Anhydrase Inhibitors chemical synthesis
Cyclooxygenase Inhibitors chemical synthesis
Imides chemistry
Sulfonamides chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 84
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30508771
- Full Text :
- https://doi.org/10.1016/j.bioorg.2018.11.033