Novel candidates synthesis of indenopyrazole, indenoazine and indenothiophene, with anticancer and <i>in silico</i> studies
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<b>Aim:</b> The indandione nucleus, is one of the most amazing nuclei in medicinal chemistry, is used to design new derivatives. <b>Methods & materials:</b> Novel indandione derivatives are prepared with different electrophilic and nucleophilic reagents to yield <b>3</b>, <b>4</b>, <b>8</b>, <b>11</b>, <b>14</b>, <b>16, 19, 20, 21, 22</b> and <b>23</b>. Compounds <b>8, 11, 16, 20</b> and <b>23</b> are investigated against OVCAR-3 and HeLa, using LLC-MK2 and <i>cis</i>-Pt as references. <i>in silico</i> and spectral studies were analyzed for the selected compounds. <b>Results:</b> Compounds <b>20</b> and <b>23</b> at 100 ns were the most potent compounds, so molecular dynamics studies were performed. <b>Conclusion:</b> Compound <b>23</b> was the most active toward the HeLa cervical cell line, and compound <b>20</b> was the most active toward the Ovcar-3 cell line. The research study was carried out in our laboratory as a continuous work for heterocyclization reactions. The article represented newly synthesized compounds of indan-1,3-dione derivatives. The compounds underwent investigation against different anticancer cell lines, molecular docking, density functional theory, molecular dynamics and pharmacokinetic studies. Spectral data were carried out to illustrate the structure of the new series.
研究目的：茚二酮母核（indandione nucleus）是药物化学领域极具研究价值的母核之一，常被用于设计新型衍生物。 材料与方法：采用不同亲电、亲核试剂制备新型茚二酮衍生物，得到化合物3、4、8、11、14、16、19、20、21、22及23。选取化合物8、11、16、20及23针对OVCAR-3与海拉（HeLa）细胞开展活性测试，以LLC-MK2细胞与顺铂（cis-Pt）作为对照，并对所选化合物进行计算机模拟（in silico）与光谱学分析。 研究结果：在100纳秒的测试条件下，化合物20与23的活性最为显著，因此对二者开展了分子动力学（molecular dynamics）研究。 研究结论：化合物23对海拉宫颈癌细胞系的抑制活性最强，而化合物20对OVCAR-3卵巢癌细胞系的抑制活性最优。 本研究为本实验室杂环化反应系列研究的延续工作。本文报道了一系列新合成的茚烷-1,3-二酮（indan-1,3-dione）衍生物，对其开展了多种抗肿瘤细胞系活性测试、分子对接、密度泛函理论（density functional theory）、分子动力学与药代动力学研究，并通过光谱数据阐明了该系列新化合物的化学结构。
