In the search for new drugs, strategies such as bioisosterism have been evidenced, in which the modification of molecules is already known to be active. Thus, metal complexes of known drugs have been highlighted, with examples of significant improvements in therapeutic efficacy. In this way, this work aimed at the synthesis of new zinc complexes with nonsteroidal anti-inflammatory drugs (NSAIDs), as well as the chemical characterization and the previous toxicity by cytotoxicity with Artemia salina, and evaluating the ability of these compounds to interact with DNA. As result, two new zinc II ternary complexes containing the NSAIDs diclofenac (Diclof) and ibuprofen (Ibup) and nicotinamide neutral linker (Nic) were obtained by the two-step solvent metal-ligand complexation method. Molecular structures were determined by NMR, FTIR, HR-MS, UV-Vis and X-ray diffraction, which demonstrated that both complexes are binuclear systems of general formula [Zn2(R-COO-)4(Nic)2]. Plasmidial DNA breakdown capacities were evaluated by producing single and double breaks (DNA FII and FIII) from plasmid incubation with complex solutions in the concentration range 0 to 400 μmol·L-1 in experiments with the presence and absence of light. Both experiments did not show significant differences (P ≤ 0.05) in induced DNA cleavage activity between the maximum study concentrations (400 μmol·L-1) and the negative controls for both complexes. The types of complex 1 and 2 interactions with the secondary DNA structure were determined by titrating a CT-DNA solution with complex solutions and monitored by circular dichroism spectrometry. The results showed that both complexes interact with the grooves of the secondary structure of CT-DNA by electrostatic attraction, but without evidence of alteration in the primary structure. Acute toxicity tests against Artemia salina showed that both complexes did not produce lethality >10% of the population up to a maximum concentration of 1200 μg·mL-1 within an exposure interval of 24 h. Thus, two new compounds were synthesized, characterized and had their previous toxicities determined. These compounds are promising new drugs, with the next step being evaluations of their activity.

中文翻译：

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作为环加氧酶抑制剂原型的新型双氯芬酸和布洛芬锌（II）-烟酰胺三元复合物的合成，化学表征和DNA相互作用研究。

在寻找新药时，已经证明了诸如生物立体异构的策略，其中已知分子的修饰是有效的。因此，已经突出了已知药物的金属配合物，并列举了治疗功效的显着改善。这样，这项工作旨在合成具有非甾体抗炎药（NSAIDs）的新锌配合物，以及化学鉴定和先前对卤虫卤虫的细胞毒性所产生的毒性，并评估这些化合物与锌的相互作用。脱氧核糖核酸。结果，通过两步溶剂金属-配体络合方法获得了含有NSAIDs双氯芬酸（Diclof）和布洛芬（Ibup）和烟酰胺中性接头（Nic）的两种新的锌II三元复合物。分子结构通过NMR，FTIR，HR-MS，UV-Vis和X射线衍射表明这两种络合物均为通式[Zn2（R-COO-）4（Nic）2]的双核体系。通过在有光和无光的实验中，用浓度范围为0至400μmol·L-1的复杂溶液温育质粒产生单断裂和双断裂（DNA FII和FIII）来评估质粒DNA的分解能力。两种复合物的最大研究浓度（400μmol·L-1）与阴性对照之间，在诱导的DNA裂解活性方面均未显示出显着差异（P≤0.05）。通过用复杂溶液滴定CT-DNA溶液来确定与二级DNA结构发生的复杂1和2相互作用的类型，并通过圆二色谱法进行监测。结果表明，两种复合物均通过静电吸引作用与CT-DNA二级结构的凹槽相互作用，但没有证据表明一级结构发生改变。对卤虫的急性毒性试验表明，在24小时的暴露间隔内，最高浓度为1200μg·mL-1时，两种复合物都不会产生大于总种群10％的致死率。因此，合成了两种新化合物，对其进行了表征并确定了其先前的毒性。这些化合物是有前途的新药，下一步是对其活性的评估。在24小时的暴露时间间隔内，有10％的人群达到最大浓度1200μg·mL-1。因此，合成了两种新化合物，对其进行了表征并确定了其先前的毒性。这些化合物是有前途的新药，下一步是对其活性的评估。在24小时的暴露时间间隔内，有10％的人群达到最大浓度1200μg·mL-1。因此，合成了两种新化合物，对其进行了表征并确定了其先前的毒性。这些化合物是有前途的新药，下一步是对其活性的评估。