Abstract：
The interaction of deoxyribonucleic acid (DNA) with medicinally significant small molecules has long piqued the interest of researchers because its applications are directly related to the discovery of new classes of drugs. Keeping this in mind, here we report berberine derivatives and their interaction with calf thymus DNA (CT-DNA). In this report we discussed on the structural perspectives and thermodynamic characteristics of the interaction of four 9-O-substituted berberines (BRDR1 to BRDR4) with CT-DNA. The binding affinity of BRDR-DNA complexes increased with increasing the cycloalkane ring size of the substitution except BRDR2. The binding constant value obtained from UV-Visible spectral analysis was 1.12 × 106 for BRDR1, 0.37 × 106 for BRDR2, 1.72 × 106 for BRDR3 and 3.20 × 106 for BRDR4. Ferrocyanide quenching experiments revealed unequivocally that the analogues except BRDR2 had a partly intercalative binding to DNA. From the ITC experiment it was found that the bindings of BRDR1, BRDR3 and BRDR4 to DNA was favoured by negative enthalpy and positive entropy while BRDR2 was driven by positive enthalpy and positive entropy. In all cases the hydrophobic interaction plays a crucial role. Thus, the complete multispectroscopic and thermodynamic binding studies may be useful for new drug design and development.Communicated by Ramaswamy H. Sarma.
摘要：
脱氧核糖核酸（DNA）与医学上重要的小分子的相互作用长期以来引起了研究人员的兴趣，因为它的应用与新类药物的发现直接相关。记住这一点，在这里，我们报道小檗碱衍生物及其与小牛胸腺DNA（CT-DNA）的相互作用。在本报告中，我们讨论了四种9-O-取代的小檗碱（BRDR1至BRDR4）与CT-DNA相互作用的结构观点和热力学特征。BRDR-DNA复合物的结合亲和力随着取代的环烷烃环大小的增加而增加，BRDR2除外。从紫外可见光谱分析获得的结合常数对于BRDR1为1.12×106，对于BRDR2为0.37×106，对于BRDR3为1.72×106，对于BRDR4为3.20×106。亚铁氰化物猝灭实验明确表明，除BRDR2以外的类似物与DNA具有部分嵌入性结合。从ITC实验中发现，负焓和正熵有利于BRDR1，BRDR3和BRDR4与DNA的结合，而BRDR2则由正焓和正熵驱动。在所有情况下,疏水相互作用都起着至关重要的作用。因此，完整的多光谱和热力学结合研究可能对新药设计和开发有用。由RamaswamyH.Sarma沟通。
