Siddiqui Rubina, Shamim Sana, Akhter Shamim, Kausar Samia, Yousuf Sammer, Ali Altaf Ataf, Saeed Saify Zafar, Ameen Fuad
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical, Sciences, University of Karachi, Karachi, 75270, Pakistan.
Department of Pharmaceutical Chemistry, Dow College of Pharmacy, Faculty of Pharmaceutical Sciences, Dow University of Health Sciences, Ojha Campus, Karachi, Pakistan.
Heliyon. 2024 Jul 25;10(15):e35122. doi: 10.1016/j.heliyon.2024.e35122. eCollection 2024 Aug 15.
Inflammation is one of the pertinent responses of the body, depending mainly on the process and factors involved in combating the oxidative species produced either by any infection or failure of the antioxidant pathways. In search of new compounds to exhibit antioxidant and anti-inflammatory activity here, we have successfully reported the synthesis of three novel compounds of Piperidin-4-one skeleton by adopting simple and convenient methods. Compound , (3, 3-dimethyl-2, 6-bis(3,4,5-trimethoxyphenyl) piperidin-4-one) was synthesized by one-pot Mannich condensation reaction having good yield (88 %). Furthermore in the next step highly functionalized imine derivatives, Compound (3,3-dimethyl-2,6-bis (3,4,5-trimethoxyphenyl) piperidine-4-one) hydrazine carbothioamide) and Compound (3,3-dimethyl-2,6-bis(3,4,5-trimethoxyphenyl) piperidin-4-one oxime) were prepared by the condensation reaction with thiosemicarbazide and hydroxylamine hydrochloride with compound , respectively. The structure of the compounds has been deduced by the combined use of modern spectroscopic and single crystal x-ray diffraction (XRD) techniques. ADMET studies predict pharmacokinetic properties and showed that compounds are non toxic on vital organs. The optimized geometry and reactivity parameters of compounds were further calculated based on the B3LYP/6-31G (d, p) density functional theory (DFT). The negative values of chemical potential follow the trend as (-0.2101) > (-0.2198) > (-0.2233) signifies that all compounds are reactive in nature as evident from antioxidant and anti-inflammatory response were determined by using the DDPH assay and protein denaturation methods respectively. Compounds possess good radical scavenging activity having IC 50 values 30.392 μM (), 37.802 () μM, and 72.285 () μM, and anti-inflammatory response in same manner indicating that (71.3 %) is more active than compound (43.5 %) and (39.3 %) marking them as a potential antioxidant and anti-inflammatory agents.
炎症是机体的相关反应之一，主要取决于对抗由任何感染或抗氧化途径失败所产生的氧化物质的过程和因素。为了寻找具有抗氧化和抗炎活性的新化合物，我们采用简单便捷的方法成功报道了三种新型哌啶 - 4 - 酮骨架化合物的合成。化合物（3,3 - 二甲基 - 2,6 - 双（3,4,5 - 三甲氧基苯基）哌啶 - 4 - 酮）通过一锅法曼尼希缩合反应合成，产率良好（88%）。此外，在下一步中，分别通过与硫代氨基脲和盐酸羟胺与化合物进行缩合反应，制备了高官能化的亚胺衍生物，化合物（3,3 - 二甲基 - 2,6 - 双（3,4,5 - 三甲氧基苯基）哌啶 - 4 - 酮肼基硫代甲酰胺）和化合物（3,3 - 二甲基 - 2,6 - 双（3,4,5 - 三甲氧基苯基）哌啶 - 4 - 酮肟）。通过结合使用现代光谱学和单晶X射线衍射（XRD）技术推断了化合物的结构。ADMET研究预测了药代动力学性质，表明化合物对重要器官无毒。基于B3LYP/6 - 31G（d, p）密度泛函理论（DFT）进一步计算了化合物的优化几何结构和反应性参数。化学势的负值遵循（ - 0.2101）>（ - 0.2198）>（ - 0.2233）的趋势，这表明所有化合物本质上都具有反应性，从抗氧化和抗炎反应分别通过DDPH测定法和蛋白质变性方法确定可以明显看出。化合物具有良好的自由基清除活性，IC50值分别为30.392 μM（）、37.802（）μM和72.285（）μM，并且以相同方式具有抗炎反应，表明（71.3%）比化合物（43.5%）和（39.3%）更具活性，使其成为潜在的抗氧化和抗炎剂。
