DNA can adopt various distinct structural motifs, such as quadruplex, duplex, i-motifs, etc. which have multifarious applications in biomedical therapeutics. Quadruplex-duplex hybrids (QDHs) consist of the juxtaposed quadruplex and duplex motifs and are thermally stable and biologically relevant. Selective binding toward these secondary structures plays an important role in the evaluation of the structure-specific ligands. Herein, several small molecules containing anthraquinone conjugated oligopyrrole, oligoimidazole, and pyrrole-imidazole derivatives have been screened for the binding of the quadruplex-duplex nucleic acid hybrids formed in PIM1 sequences through docking and molecular dynamics (MD) simulation studies. The binding interaction of the anthraquinone polypyrrole ligands has also been checked by performing different biophysical experiments. PIM1, being a coactivator of the MYC oncogene, can be targeted by these small molecules to control MYC expression which is overexpressed in the majority of human cancer cells. Accordingly, these cancer cell-specific and blood-compatible anthraquinone conjugated oligopyrrole ligands can be employed for anticancer therapeutic applications. Thus, the structure–activity relationship (SAR) of the screened ligands manifested prudent structural information for designing PIM1 QDHs targeting small molecules.

中文翻译：

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合成吡咯-咪唑甲酰胺药物靶向 PIM1 序列杂合核酸结构的化学信息和计算模型

DNA 可以采用各种不同的结构基序，例如四链体、双链体、i-基序等，它们在生物医学治疗学中具有多种应用。四链体-双链体杂交体 (QDH) 由并列的四链体和双链体基序组成，具有热稳定性和生物学相关性。对这些二级结构的选择性结合在结构特异性配体的评估中起着重要作用。在此，已经筛选了几种含有蒽醌缀合的低聚吡咯、低聚咪唑和吡咯-咪唑衍生物的小分子，用于结合PIM1中形成的四链体-双链体核酸杂交体通过对接和分子动力学 (MD) 模拟研究序列。蒽醌聚吡咯配体的结合相互作用也通过不同的生物物理实验进行了检查。PIM1作为MYC致癌基因的共激活因子，可被这些小分子靶向以控制在大多数人类癌细胞中过度表达的MYC表达。因此，这些癌细胞特异性和血液相容性蒽醌缀合的低聚吡咯配体可用于抗癌治疗应用。因此，筛选出的配体的构效关系 (SAR) 显示了设计针对小分子的PIM1 QDH 的审慎结构信息。