Shaheen Kosar, Alam Aftab, Elhenawy Ahmed A, Khan Irfan Amir, Rahman Fayaz Ur, Ali Abid, Rehman Munir Ur, AlAsmari Abdullah F, Alasmari Fawaz, Ahmad Manzoor, Khan Momin
Department of Chemistry, Abdul Wali Khan University, Mardan, Khyber Pakhtunkhwa, 23200, Pakistan.
Department of Chemistry, Rawalpindi Women University, Rawalpindi, Pakistan.
Sci Rep. 2025 Aug 9;15(1):29144. doi: 10.1038/s41598-025-13351-2.
Improving anti-inflammatory and analgesic drugs with negligible adverse effects remains a significant challenge for long-term use. In the present study, flurbiprofen-based oxadiazole derivatives were synthesized and evaluated for their in vivo anti-inflammatory activity using the carrageenan-induced paw edema assay in mice. Amongst the tested compounds, 10, 3, and 5 exhibited remarkable anti-inflammatory activity, with edema inhibition rates of 88.33%, 66.66%, and 55.55% respectively, compared to the standard drug flurbiprofen, which showed a 90.01% reduction. Molecular docking studies confirmed stable interactions of these compounds with the COX-2 binding site, similar to those observed with the standard drug flurbiprofen. Moreover, toxicity predictions, ADME profiles, and bioactivity scores were evaluated, along with frontier molecular orbitals (HOMO and LUMO) and the molecular electrostatic potential maps (MEP), to reveal the compounds' drug-like properties and chemically reactive regions. These findings highlight the potential of these derivatives as promising candidates for further development as anti-inflammatory agents.
开发副作用可忽略不计的抗炎和镇痛药仍然是长期使用面临的重大挑战。在本研究中,合成了基于氟比洛芬的恶二唑衍生物,并使用角叉菜胶诱导的小鼠爪肿胀试验评估其体内抗炎活性。在所测试的化合物中,10、3和5表现出显著的抗炎活性,与标准药物氟比洛芬(其肿胀抑制率为90.01%)相比,其肿胀抑制率分别为88.33%、66.66%和55.55%。分子对接研究证实这些化合物与COX-2结合位点存在稳定相互作用,类似于标准药物氟比洛芬的情况。此外,还评估了毒性预测、ADME特性和生物活性评分,以及前沿分子轨道(HOMO和LUMO)和分子静电势图(MEP),以揭示这些化合物的类药物性质和化学反应区域。这些发现突出了这些衍生物作为抗炎剂进一步开发的有前景候选物的潜力。