Department of Physics, Assam University, Silchar, 788 011, Assam, India.
Discipline of Natural Sciences, Indian Institute of Information Technology, Design, and Manufacturing, Dumna Airport Road, Khamaria, Jabalpur, 482005, India.
J Mol Model. 2022 Sep 5;28(10):291. doi: 10.1007/s00894-022-05304-7.
Ruthenium (Ru)-based anticancer drugs are considered to be novel alternatives of platinum-based drugs. They exhibit potent cytotoxicity against the cancer cells and hence are useful for the treatment of cancer. Herein, the density functional theory calculations in the gas phase and aqueous media are carried out to study the reactions of two Ru(III)-based drugs such as KP1019 and KP418 with the N7 site of guanine (G), 2'-deoxyguanosine (dGua), and guanosine (Gua) to understand their reactivity against the DNA and RNA. All the reactions are found to be exothermic. The activation free energies and rate constants of these reactions indicate that KP1019 and KP418 would react with the dGua more readily than Gua. Hence, the binding of these drugs with the DNA would be more preferred as compared to RNA. It is further found that among these drugs, KP1019 would be more reactive than KP418 in agreement with the experimental observation. Thus, this study is expected to aid in the future development of potent anticancer drugs.
钌（Ru）类抗癌药物被认为是铂类药物的新型替代品。它们对癌细胞表现出很强的细胞毒性，因此可用于癌症治疗。本文在气相和水相介质中通过密度泛函理论计算，研究了两种 Ru(III)类药物 KP1019 和 KP418 与鸟嘌呤（G）、2'-脱氧鸟苷（dGua）和鸟苷（Gua）的 N7 位的反应，以了解它们对 DNA 和 RNA 的反应活性。所有反应均为放热反应。这些反应的活化自由能和速率常数表明，KP1019 和 KP418 与 dGua 的反应比 Gua 更容易。因此，与 RNA 相比，这些药物与 DNA 的结合更受青睐。进一步发现，这些药物中，KP1019 的反应活性比 KP418 更强，这与实验观察结果一致。因此，这项研究有望有助于未来开发更有效的抗癌药物。
