A computational insight on the noncovalent interactions of aminothiazole-based palladium(II) complexes with DNA as a potent anticancer agent

In recent times, cancer has been reported as one of the largest growing deadly diseases in humankind. The use of cisplatin for oncological treatment has been known for a long time. However, no other suitable solutions have been extensively explored to substitute highly potent yet toxic cisplatin. In the current work, we have computationally investigated five experimentally synthesized Pd(II) complexes (Nn, n = 1-5), along with their positively charged aqua derivatives (NnW, n = 1-5), having aminothiazole analogues that may act as a potent inhibitor(s) of cancer. The interaction of the Pd(II) complexes with the B-DNA (1BNA) and preformed intercalation site DNA (1XRW) was explored by implementing the molecular docking with clustering protocol to generate the most probable docked conformers. From the docking analyses, we found that the Pd(II) complexes bind to the minor groove of the DNA in a parallel fashion. Moreover, the results suggested that the minor groove binding moderately dominates the intercalation mode of binding besides having aromatic rings. The results also implied that the aqua derivatives of the Pd(II) complexes undergo strong binding (both minor groove and intercalation) due to the higher positive charge than their corresponding chloride derivatives. Furthermore, the aqua complexes with fluorinated aromatic rings (N1W and N5W) have a lower binding affinity for intercalation than for binding in the minor groove. Additionally, we performed the independent gradient model (IGM) analysis for the minor groove binding only from the first seed of the most probable docked conformers, for which our study confirmed the presence of hydrogen bonding and van der Waals interactions. Altogether, our results provide good insights into the fate of the chosen complexes and may act as a potent alternative(s) to cisplatin.