Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
J Biomol Struct Dyn. 2021 Feb;39(3):970-976. doi: 10.1080/07391102.2020.1722240. Epub 2020 Feb 12.
Aminophylline (Am) is a methylxanthine compound clinically applied for chronic lung diseases like asthma, bronchitis or emphysema. Chemically, it comprises theophylline and ethylenediamine in a ratio 2:1. For the widening of the therapeutic window of any class of drug or for the designing of the newer therapeutic compound, an insight into the binding mechanics of available drugs with DNA is quite imperative. In view of that, here in this study we have investigated binding mechanics of aminophylline molecule with calf thymus DNA (Ct-DNA) using various spectroscopic techniques as well as molecular docking approach. Spectral analysis employing UV-visible and fluorescence approach confirmed the formation of aminophylline-Ct-DNA complex. The binding constant was calculated as 3.5 × 10 M with 0.90 as the value of binding site suggestive of minor groove binding mode of aminophylline. The groove binding mode was further confirmed through spectrofluorimetric experiments like competitive displacement assay employing ethidium bromide, hoechst and rhodamine 6 G dyes as well as iodide quenching studies. The circular dichroic spectral evaluation and molecular docking study finally validated the minor groove binding mode of aminophylline with binding energy calculated as -4.5 Kcal/mol.
氨茶碱（Am）是一种临床上用于治疗哮喘、支气管炎或肺气肿等慢性肺部疾病的甲基黄嘌呤化合物。从化学角度来看，它由茶碱和乙二胺以 2:1 的比例组成。为了拓宽任何一类药物的治疗窗口，或者为了设计新的治疗化合物，深入了解现有药物与 DNA 的结合机制是非常必要的。有鉴于此，在这项研究中，我们使用各种光谱技术以及分子对接方法研究了氨茶碱分子与小牛胸腺 DNA（Ct-DNA）的结合力学。光谱分析采用紫外可见和荧光方法证实了氨茶碱-Ct-DNA 复合物的形成。结合常数计算为 3.5×10 M，结合位点值为 0.90，表明氨茶碱的结合模式为小沟结合模式。通过竞争性置换实验，如溴化乙锭、hoechst 和罗丹明 6G 染料以及碘离子猝灭研究，进一步证实了小沟结合模式。圆二色光谱评估和分子对接研究最终验证了氨茶碱与结合能为-4.5 Kcal/mol 的小沟结合模式。
