Tabassum Nazifa, Spriha Sabiha Enam, Saha Poushali, Rahman Fahad Imtiaz, Hossain A S M Monjur Al, Rahman S M Abdur
Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, Bangladesh.
Department of Pharmaceutical Technology, University of Dhaka, Dhaka, 1000, Bangladesh.
Heliyon. 2024 Nov 22;10(23):e40630. doi: 10.1016/j.heliyon.2024.e40630. eCollection 2024 Dec 15.
Six heteroarylamide derivatives were synthesized in good yields and screened for several biological activities. Compounds demonstrated analgesic activity with percentage inhibition of writhing between 77.10 and 95.79 %, comparable to that of the standard aceclofenac having 91.12 % writhing inhibition. Evaluation of anti-inflammatory activity unveiled that compound exhibited 36.9 %, 64.17 %, 82.9 % and 93.9 % inhibition of paw edema as compared to aceclofenac's inhibition of 35.5 %, 78.6 %, 79.3 % and 91.2 % at the 1st, 2nd, 3rd and 4th hours, respectively. Compounds and exerted considerable antidiarrheal effects with 85.00 % and 71.67 % inhibition of defecation at 25 mg/kg dose, respectively, whereas, the standard loperamide showed 85.00 % inhibition. Compounds manifested promising activity in brine shrimp lethality bioassay as well as in trypan blue dye exclusion assay, resulting in 10-20 % cell viability on HeLa cell line and compound was found to have the lowest IC of 281.96 μM in the MTT assay. Molecular docking analysis suggested that certain macromolecular targets such as cyclooxygenase-2, muscarinic M3 receptor and matrix metalloproteinase 9 (MMP9) might be involved for the observed activities. As predicted by ADME/T analysis, the compounds also possessed good pharmacokinetic properties.
合成了六种杂芳基酰胺衍生物，产率良好，并对其进行了多种生物活性筛选。化合物表现出镇痛活性，扭体抑制率在77.10%至95.79%之间，与标准醋氯芬酸（扭体抑制率为91.12%）相当。抗炎活性评估表明，与醋氯芬酸在第1、2、3和4小时分别对爪肿胀的抑制率35.5%、78.6%、79.3%和91.2%相比，化合物对爪肿胀的抑制率分别为36.9%、64.17%、82.9%和93.9%。化合物和在25mg/kg剂量下分别表现出显著的止泻作用，排便抑制率分别为85.00%和71.67%，而标准洛哌丁胺的排便抑制率为85.00%。化合物在卤虫致死生物测定以及台盼蓝染料排斥试验中表现出有前景的活性，在HeLa细胞系上导致10 - 20%的细胞活力，并且在MTT试验中发现化合物的最低半数抑制浓度为281.96μM。分子对接分析表明，某些大分子靶点如环氧化酶 - 2、毒蕈碱M3受体和基质金属蛋白酶9（MMP9）可能与观察到的活性有关。正如ADME/T分析所预测的，这些化合物还具有良好的药代动力学性质。
