Yasmin Farah, Nazli Zill-I-Huma, Shafiq Nusrat, Aslam Maryam, Bin Jardan Yousef A, Nafidi Hiba-Allah, Bourhia Mohammed
Synthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad 38000, Pakistan.
Department of Chemistry, Government College Women University, Faisalabad 38000, Pakistan.
ACS Omega. 2023 Aug 28;8(36):32677-32689. doi: 10.1021/acsomega.3c03342. eCollection 2023 Sep 12.
is an attractive, ever-blossoming, and effortlessly available plant around the globe. The fabulous flowers of enjoy a significant status in folk medicine throughout the world and comprise a range of phyto constituents due to which this splendid flower owns numerous biological and pharmaceutical activities like antioxidant, antifungal, antimicrobial, anti-inflammatory, antipyretic, antidiabetic, and antifertility activity. Considering this, column chromatographic isolation of the phytoconstituents of ethyl acetate fraction of the flowers of was performed. A series of five phthalates including Di--octyl phthalate (), ditridecyl phthalate (), 1-allyl 2-ethyl phthalate (), diethyl phthalate (), and bis (6-methylheptyl) phthalate () were isolated. The structures of the isolated phthalates were elucidated by gas chromatography-mass spectrometry, H NMR, and C NMR. In silico and in vitro antidiabetic and antioxidant potential and DFT studies of isolated phthalates were carried out. In our study, isolated ligands were explored as potent antidiabetic as well as antioxidant agents as they exhibited good binding affinity (in in vitro and in silico experiments) against all selected protein targets. Compounds showed that the binding affinity value ranged from -5.9 to -5.2 kcal/mol, -5.5 to -4.3 kcal/mol, and -5.0 to -4.1 kcal/mol for target proteins 1HNY, 2I3Y, and 5O40, respectively. Among all isolated phthalates, can be a lead compound as it showed the best binding affinity with human pancreatic α-amylase (Δ = -5.9 kcal/mol) and displayed a minimum inhibition concentration (IC) of 11.69 μM among all phthalates. Compound was the best docked and scored compound for inhibiting glutathione peroxidase; however, possessed the lowest binding score of -5.0 kcal/mol, thus indicating the highest potential among isolated phthalates for inhibiting the superoxide dismutase. Furthermore, the top-ranked docked ligand-protein complex for each protein was assessed for stability of protein and complex mobility by molecular dynamics simulation using the IMOD server.
是一种在全球范围内具有吸引力、四季开花且极易获取的植物。其迷人的花朵在世界各地的民间医学中享有重要地位，并且含有一系列植物成分，正因如此，这种绚丽的花朵拥有众多生物和药学活性，如抗氧化、抗真菌、抗菌、抗炎、解热、抗糖尿病和抗生育活性。考虑到这一点，对该植物花朵乙酸乙酯部位的植物成分进行了柱色谱分离。分离出了一系列五种邻苯二甲酸酯，包括邻苯二甲酸二异辛酯（）、邻苯二甲酸二正十三烷基酯（）、邻苯二甲酸1-烯丙基2-乙酯（）、邻苯二甲酸二乙酯（）和邻苯二甲酸双（6-甲基庚基）酯（）。通过气相色谱-质谱联用、氢核磁共振（H NMR）和碳核磁共振（C NMR）对分离出的邻苯二甲酸酯的结构进行了阐明。对分离出的邻苯二甲酸酯进行了计算机模拟和体外抗糖尿病及抗氧化潜力以及密度泛函理论（DFT）研究。在我们的研究中，所分离出的配体被探索为有效的抗糖尿病和抗氧化剂，因为它们在体外和计算机模拟实验中对所有选定的蛋白质靶点都表现出良好的结合亲和力。化合物对目标蛋白1HNY、2I3Y和5O40的结合亲和力值分别为-5.9至-5.2千卡/摩尔、-5.5至-4.3千卡/摩尔和-5.0至-4.1千卡/摩尔。在所有分离出的邻苯二甲酸酯中，可作为先导化合物，因为它与人类胰腺α-淀粉酶显示出最佳结合亲和力（Δ = -5.9千卡/摩尔），并且在所有邻苯二甲酸酯中显示出最低抑制浓度（IC）为11.69微摩尔。化合物是抑制谷胱甘肽过氧化物酶的最佳对接和评分化合物；然而，具有最低的结合分数-5.0千卡/摩尔，因此表明在分离出的邻苯二甲酸酯中具有抑制超氧化物歧化酶的最高潜力。此外，使用IMOD服务器通过分子动力学模拟评估了每种蛋白质的排名靠前的对接配体-蛋白质复合物的蛋白质稳定性和复合物流动性。
