Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions.
Bioorg Chem
; 84: 260-268, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30508771
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 (ED50) of 34.3-49.8â¯mgâ¯kg-1 and 63.6-86.6% edema inhibition relative to the reference drug celecoxib (ED50 33.9â¯mgâ¯kg-1 and 85.2% edema inhibition). Compounds 6-11 and 18 were weakly cytotoxic at 10⯵M 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)â¯>â¯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 KI ranges were 54.1-81.9â¯nM for hCA I, 25.9-55.1â¯nM for hCA II, and 46.0-348.3â¯nM for hCA IX. © 2018 Elsevier Science. All rights reserved.
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01-internacional
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MEDLINE
Assunto principal:
Sulfonamidas
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Inibidores da Anidrase Carbônica
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Inibidores de Ciclo-Oxigenase
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Imidas
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Anti-Inflamatórios
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article