Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutics; they are competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the conversion of arachidonic acid to inflammatory prostaglandins.

Objective: In this study, new benzodioxol derivatives with different core cycles and functional groups (i.e., aryl acetate, aryl acetic acid and diazepine) were designed, synthesized, identified and evaluated for their analgesic and anti-inflammatory activity, as a preliminary screening study to identify the most potent and more selective groups.

Methods: The synthesized compounds were identified using FTIR, HRMS, 1H-NMR and 13C-NMR, and evaluated for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay kit.

Results and Discussion: Six compounds were synthesized as a preliminary screening study to identify which was the most potent and more selective group towards COX-2 versus COX-1, compared to ketoprofen as non-selective NSAIDs. The compounds have three different groups: aryl acetate, aryl acetic acid and diazepine. The results showed that the most potent compound against the COX- 1 enzyme was 4b (which has diazepine and 2-chlorophenyl) with IC50 = 0.363 μM, and the selectivity ratio of 4b was found to be better than ketoprofen. In contrast, compound 4a (which has diazepine and 3-chlorophenyl) was the most selective with a COX-1/COX-2 ratio value of 0.85 in comparison with a ketoprofen ratio value of 0.20.

Conclusion: In general, the synthesized library has moderate activity against both enzymes (i.e., COX-1 and COX-2). Moreover, all six compounds have better COX-2 inhibition selectivity compared to the commercial drug ketoprofen.

中文翻译：

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苯并二恶唑衍生物作为环氧合酶抑制剂的合成及生物学评价

背景：非甾体类抗炎药（NSAIDs）是使用最广泛的疗法之一。它们是环氧合酶（COX）的竞争性抑制剂，环氧合酶介导花生四烯酸向炎性前列腺素的转化。

目的：在本研究中，设计，合成，鉴定和评估具有不同核心周期和官能团（即乙酸芳基酯，芳基乙酸和二氮杂pine）的新苯并二恶唑衍生物的镇痛和抗炎活性，作为初步筛选研究以确定最有效和更具选择性的群体。

方法：使用FTIR，HRMS，1H-NMR和13C-NMR鉴定合成的化合物，并使用体外环氧合酶（COX）抑制测定试剂盒评估其对绵羊COX-1和COX-2的抑制活性。

结果与讨论：合成了六种化合物作为初步筛选研究，以鉴定与酮洛芬相比作为非选择性NSAID，与COX-1相比，哪种化合物对COX-2的作用最强，选择性最高。这些化合物具有三个不同的组：乙酸芳基酯，乙酸芳基酯和二氮杂pine。结果表明，对COX-1酶最有效的化合物是4b（具有二氮杂和2-氯苯基），IC50 = 0.363μM，发现4b的选择性比酮洛芬更好。相反，与酮洛芬比率值为0.20相比，化合物4a（具有二氮杂和3-氯苯基）的选择性最高，COX-1 / COX-2比率值为0.85。

结论：通常，合成文库对两种酶（即COX-1和COX-2）具有中等活性。此外，与市售药物酮洛芬相比，所有六个化合物均具有更好的COX-2抑制选择性。