Pasricha Sharda, Sharma Deepti, Ojha Himanshu, Gahlot Pragya, Pathak Mallika, Basu Mitra, Chawla Raman, Singhal Sugandha, Singh Anju, Goel Rajeev, Kukreti Shrikant, Shukla Shefali
Department of Chemistry, Sri Venkateswara College, University of Delhi, Delhi, India.
Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Luminescence. 2017 Nov;32(7):1252-1262. doi: 10.1002/bio.3319. Epub 2017 May 16.
Chalcones possess various biological properties, for example, antimicrobial, anti-inflammatory, analgesic, antimalarial, anticancer, antiprotozoal and antitubercular activity. In this study, naphthylchalcone derivatives were synthesized and characterized using H NMR C NMR, Fourier transform infrared and mass techniques. Yields for all derivatives were found to be >90%. Protein-drug interactions influence the absorption, distribution, metabolism and excretion (ADME) properties of a drug. Therefore, to establish whether the synthesized naphthylchalcone derivatives can be used as drugs, their binding interaction toward a serum protein (bovine serum albumin) was investigated using fluorescence, circular dichroism and molecular docking techniques under physiological conditions. Fluorescence quenching of the protein in the presence of naphthylchalcone derivatives, and other derived parameters such as association constants, number of binding sites and static quenching involving confirmed non-covalent binding interactions in the protein-ligand complex were observed. Circular dichroism clearly showed changes in the secondary structure of the protein in the presence of naphthylchalcones, indicating binding between the derivatives and the serum protein. Molecular modelling further confirmed the binding mode of naphthylchalcone derivatives in bovine serum albumin. A site-specific molecular docking study of naphthylchalcone derivatives with serum albumin showed that binding took place primarily in the aromatic low helix and then in subdomain II. The dominance of hydrophobic, hydrophilic and hydrogen bonding was clearly visible and was responsible for stabilization of the complex.
查尔酮具有多种生物学特性，例如抗菌、抗炎、止痛、抗疟疾、抗癌、抗原虫和抗结核活性。在本研究中，使用核磁共振氢谱（¹H NMR）、核磁共振碳谱（¹³C NMR）、傅里叶变换红外光谱和质谱技术合成并表征了萘基查尔酮衍生物。发现所有衍生物的产率均>90%。蛋白质-药物相互作用会影响药物的吸收、分布、代谢和排泄（ADME）特性。因此，为了确定合成的萘基查尔酮衍生物是否可用作药物，在生理条件下使用荧光、圆二色性和分子对接技术研究了它们与血清蛋白（牛血清白蛋白）的结合相互作用。观察到在萘基查尔酮衍生物存在下蛋白质的荧光猝灭，以及其他衍生参数，如缔合常数、结合位点数量和涉及蛋白质-配体复合物中已确认的非共价结合相互作用的静态猝灭。圆二色性清楚地表明在萘基查尔酮存在下蛋白质二级结构发生了变化，表明衍生物与血清蛋白之间存在结合。分子建模进一步证实了萘基查尔酮衍生物在牛血清白蛋白中的结合模式。萘基查尔酮衍生物与血清白蛋白的位点特异性分子对接研究表明，结合主要发生在芳香族低螺旋区域，然后是亚结构域II。疏水、亲水和氢键作用的主导地位清晰可见，并且是复合物稳定的原因。
