In vitro DNA binding, pBR322 cleavage and molecular docking studies of 1,2-diaminobenzene, dichloro glycyl glycinate tin(IV) and zirconium(IV) complexes

De novo design and synthesis of complexes 1,2-diaminobenzene, dichloro glycyl glycinate tin(IV) and zirconium(IV), 1 and 2 as molecular drug entities were carried out. The structure elucidation of 1 and 2 was done by analytical techniques and spectroscopic methods viz. IR, UV–vis, 1H, 13C, 119Sn NMR, ESI–Mass and XRD techniques. In vitro DNA binding studies of 1 and 2 by various biophysical techniques viz electronic absorption, emission spectroscopy and circular dichroism measurements were carried out to evaluate their potential to act as chemotherapeutic candidates; furthermore, cleavage studies with pBR322plasmid DNA and computer-aided molecular docking studies were also done to study the mechanistic pathway and mode of binding at the molecular level. The observed results revealed that complex 1 exhibited greater DNA binding propensity in contrast to complex 2 primarily via electrostatic binding mode. The pBR322 DNA cleavage studies of both the complexes revealed the hydrolytic cleavage mechanism and DNA minor groove binding, which was ascertained by molecular docking studies of the drug candidate. Communicated by Ramaswamy H. Sarma

本研究针对两种作为分子药物实体的配合物（分别为1,2-二氨基苯二氯甘氨酰甘氨酸合锡(IV)与1,2-二氨基苯二氯甘氨酰甘氨酸合锆(IV)，编号为1和2）开展了从头设计(de novo design)与合成。通过分析技术与光谱手段——即红外光谱(IR)、紫外-可见吸收光谱(UV–vis)、氢核磁共振谱(1H NMR)、碳核磁共振谱(13C NMR)、锡核磁共振谱(119Sn NMR)、电喷雾电离质谱(ESI–Mass)以及X射线衍射(XRD)——对配合物1和2完成了结构解析。为评估二者作为化疗候选药物的潜力，采用多种生物物理技术（包括电子吸收光谱、发射光谱与圆二色性测量）对配合物1和2开展了体外DNA结合研究；此外，还通过pBR322质粒DNA裂解实验与计算机辅助分子对接研究，从分子层面探究了其作用机制与结合模式。实验结果显示，配合物1相较于配合物2展现出更强的DNA结合能力，二者主要通过静电结合模式与DNA相互作用。针对两种配合物的pBR322 DNA裂解实验结果表明，其裂解机制为水解裂解，且结合位点为DNA小沟，该结论通过候选药物的分子对接研究得到了证实。本文由Ramaswamy H. Sarma转交。