Inter University Centre for Bioscience, Kannur University , Thalassery Campus, Palayad, Kerala 670661, India.
J Chem Inf Model. 2015 Dec 28;55(12):2644-56. doi: 10.1021/acs.jcim.5b00514. Epub 2015 Nov 13.
Piperine, the bioactive phytochemical from black pepper (Piper nigrum L.), is a nontoxic natural compound exhibiting many physiological and pharmacological properties. They include antioxidant, anti-inflammatory, antimutagenic, antitumor, antiapoptotic, antigenotoxic, antiarthritic, antifungal, antimicrobial, antidepressant, anti-HBV, and gastro-protective activities. It also enhances the bioavailability of phytochemicals and drugs. The molecular mechanism of action of piperine with DNA has not yet been addressed, while its pharmacological activities have been reported. In this work we report for the first time the interaction of piperine molecule with DNA duplex. We have carried out UV-vis absorption and fluorescence spectroscopy to confirm the binding of piperine with calf thymus DNA (ctDNA). The energetics of interaction of piperine with ctDNA was monitored by isothermal titration calorimetry (ITC). Differential scanning calorimetry (DSC) and melting temperature (Tm) analysis were also performed, confirming a minor groove mode of binding of piperine with ctDNA. The binding free energy ΔG values obtained from molecular dynamics simulation studies agree well with ITC values and reveal a sequence dependent minor groove binding exhibiting a specificity toward AT rich sequences.
胡椒碱是黑胡椒（Piper nigrum L.）中的一种生物活性植物化学物质，是一种无毒的天然化合物，具有许多生理和药理特性。它们包括抗氧化、抗炎、抗突变、抗肿瘤、抗凋亡、抗原毒性、抗关节炎、抗真菌、抗菌、抗抑郁、抗乙肝和胃保护活性。它还可以提高植物化学物质和药物的生物利用度。胡椒碱与 DNA 的分子作用机制尚未解决，但其药理活性已有报道。在这项工作中，我们首次报道了胡椒碱分子与 DNA 双链体的相互作用。我们进行了紫外可见吸收和荧光光谱法来证实胡椒碱与小牛胸腺 DNA（ctDNA）的结合。等温热力学滴定（ITC）监测了胡椒碱与 ctDNA 相互作用的能量学。还进行了差示扫描量热法（DSC）和熔点（Tm）分析，证实了胡椒碱与 ctDNA 的结合模式为小沟模式。从分子动力学模拟研究中获得的结合自由能ΔG 值与 ITC 值吻合较好，揭示了序列依赖性的小沟结合，表现出对富含 AT 的序列的特异性。
