a Department of Chemistry, Science and Research Branch , Islamic Azad University , Tehran , Iran.
b Chemistry & Chemical Engineering Research Center of Iran , Tehran , Iran.
J Biomol Struct Dyn. 2018 Mar;36(4):893-905. doi: 10.1080/07391102.2017.1301273. Epub 2017 May 26.
Investigation of side effects and solubility of anticancer drugs is a major challenge in chemotherapy science. Thus, design and synthesis of cisplatin analogs with higher lipophilicity as novel water-soluble anticancer drugs is valuable. In this work, two new Pt(II) complexes were synthesized with formula cis-[Pt(NH)(amylgly)]NO and cis-[Pt(amylamine)(amylgly)]NO, where gly is penthyl glycine as an amino acid. The new compounds were synthesized and extensively characterized using analytical techniques; spectroscopic methods, and conductivity measurement. The anticancer activity of synthesized complexes was investigated against colon cancer cell line HCT116 using MTT assay and results showed excellent anticancer activity with Cc values of 36 and 270 M after 24-h incubation time for cis-[Pt(NH)(amylgly)]NO and cis-[Pt(NH-amyl)(amylgly)]NO, respectively; which is lower than that for cisplatin. These complexes were also interacted with highly polymerized calf thymus DNA and the binding mode of the complexes to CT-DNA was evaluated by fluorescence, circular dichroism, and UV spectroscopy. The calculation of binding and thermodynamic of Pt(II) complexes with CT-DNA can provide deeper insight into mechanism of the action of these types of complexes with nucleic acids. So, thermodynamic parameters were also determined according to isothermal titration. In comparison with cis-[Pt(NH)(amylgly)]NO in DNA interaction, the result show that cis-[Pt(NH-amyl)(amylgly)]NO has higher affinity with binding constant K = 8.72 mM to CT-DNA. The results indicate that cis-[Pt(amylamine)(amylgly)]NO with large and bulky aliphatic group bind to CT-DNA by different modes and covalent and groove bindings were preferred mode of interaction with DNA.
抗癌药物的副作用和溶解度的研究是化疗科学的主要挑战。因此，设计和合成具有更高亲脂性的顺铂类似物作为新型水溶性抗癌药物是有价值的。在这项工作中，合成了两种新的 Pt(II) 配合物，其化学式为 cis-[Pt(NH)(amylgly)]NO 和 cis-[Pt(amylamine)(amylgly)]NO，其中 gly 是戊基甘氨酸作为一种氨基酸。新化合物通过分析技术、光谱方法和电导率测量进行了广泛的表征。使用 MTT 测定法研究了合成配合物对结肠癌细胞系 HCT116 的抗癌活性，结果表明，在 24 小时孵育时间后，cis-[Pt(NH)(amylgly)]NO 和 cis-[Pt(NH-amyl)(amylgly)]NO 的 Cc 值分别为 36 和 270 μM，表现出优异的抗癌活性，低于顺铂。这些配合物还与高度聚合的小牛胸腺 DNA 相互作用，并通过荧光、圆二色性和紫外光谱评估了配合物与 CT-DNA 的结合模式。Pt(II) 配合物与 CT-DNA 的结合和热力学计算可以提供对这些类型的配合物与核酸相互作用机制的更深入了解。因此，也根据等温滴定法确定了热力学参数。与 cis-[Pt(NH)(amylgly)]NO 在 DNA 相互作用中的结果相比，结果表明 cis-[Pt(NH-amyl)(amylgly)]NO 与 CT-DNA 的结合常数 K 值更高，为 8.72 mM。结果表明，具有大而庞大的脂肪族基团的 cis-[Pt(amylamine)(amylgly)]NO 通过不同的模式与 CT-DNA 结合，并且共价和沟结合是与 DNA 相互作用的首选模式。
