In the current study, seven (7) aurone derivatives (ADs) were synthesized and employed to LOX and COX-2 assays, models of acetic acid-induced mice writhing, formalin-induced mice paw licking and tail immersion test to evaluate their analgesic potential at the doses of 10 mg and 20 mg/kg body weight. Molecular docking was performed to know the active binding site at both LOX and COX-2 as compared to standard drugs. Among the ADs, 2-(3,4-dimethoxybenzylidene)benzofuran-3(2)-one ()possessed optimal LOX and COX-2 inhibitory strength (= and ) as compared to standard (Zileuton = 0.08 μM, Celecoxib = 0.05 μM). Similarly in various pain models compound showed significantly (p < 0.05) highest percent analgesic potency as compared to control at a dose of 20 mg/kg i.e analgesic effect in acetic acid model, (in Phase-1) and (inPhase-2) analgesic effect in formalin pain model and analgesic response in tail immersion model. By the administration of Naloxone, the tail flicking latencies were reversed (antagonized) in all treatments. The (at 10 mg/kg and 20 mg/kg was antagonized after 90 min from ± and ± to ± and ± respectively as compared to standard Tramadol (from 17.74 ± 1.33 to 3.70 ± 0.48), showing the opiodergic receptor involvement. The molecular docking study of ADs revealed that had a higher affinity for LOX and COX-2 with docking scores of and respectively. As a whole, among the tested ADs, compound demonstrated excellent analgesic effects that may have been caused by inhibiting the LOX and COX-2 pathways.

中文翻译：

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橙酮衍生物的合成、LOX和COX-2抑制的分子对接评价及体内镇痛潜力的测定

在当前的研究中，合成了七（7）种Aurone衍生物（AD）并用于LOX和COX-2测定、乙酸诱导的小鼠扭体模型、福尔马林诱导的小鼠舔爪和尾巴浸没试验，以评估其镇痛潜力剂量为10mg和20mg/kg体重。进行分子对接以了解与标准药物相比 LOX 和 COX-2 的活性结合位点。在 AD 中，与标准品（齐留通 = 0.08 μM、塞来考昔 = 0.05 μM）相比，2-(3,4-二甲氧基亚苯亚甲基)苯并呋喃-3(2)-one () 具有最佳的 LOX 和 COX-2 抑制强度（= 和 ） ）。类似地，在各种疼痛模型中，与剂量为 20 mg/kg 的对照相比，化合物显示出显着（p < 0.05）最高百分比的镇痛效力，即在乙酸模型中的镇痛效果，（在第 1 阶段）和（在第 2 阶段）镇痛福尔马林疼痛模型的作用和尾部浸没模型的镇痛反应。通过施用纳洛酮，所有治疗中的甩尾潜伏期都被逆转（拮抗）。与标准曲马多（从 17.74 ± 1.33 到 3.70 ± 0.48）相比，（10 mg/kg 和 20 mg/kg 90 分钟后分别从 ± 和 ± 到 ± 和 ± 被拮抗，显示阿片受体参与。 AD 的对接研究表明，化合物对 LOX 和 COX-2 具有较高的亲和力，对接分数分别为 和 。途径。