PDF(Pubmed)
Abstract：
A novel series of antitumor hybrids was synthesized using 1,4-benzohydroquinone and chalcone, furane, or pyrazoline scaffolds. This were achieved through isosteric substitution of the aryl group of the chalcone β-carbon with the furanyl moiety and structural modification of the α,β-unsaturated carbonyl system. The potential antitumor activity of these hybrids was evaluated in vivo on MCF-7 breast adenocarcinoma and HT-29 colorectal carcinoma cells, demonstrating cytotoxic activity with IC50 values ranging from 28.8 to 124.6 µM. The incorporation of furan and pyrazoline groups significantly enhanced antiproliferative properties compared to their analogues and precursors (VII-X), which were inactive against both neoplastic cell lines. Compounds 4, 5, and 6 exhibited enhanced cytotoxicity against both cell lines, whereas compound 8 showed higher cytotoxic activity against HT-29 cells. Molecular docking studies revealed superior free-energy values (ΔGbin) for carcinogenic pathway-involved kinase proteins, with our in silico data suggesting that these derivatives could be promising chemotherapeutic agents targeting kinase pathways. Among all the synthesized PIBHQ compounds, derivatives 7 and 8 exhibited the best drug-likeness properties, with values of 0.53 and 0.83, respectively. ADME results collectively suggest that most of these compounds hold promise as potential candidates for preclinical assays.
摘要：
使用1,4-苯醌和查尔酮合成了一系列新型的抗肿瘤杂种，呋喃,或吡唑啉支架。这是通过查尔酮β-碳的芳基与呋喃基部分的等排取代和α的结构修饰来实现的，β-不饱和羰基体系。在MCF-7乳腺癌和HT-29结直肠癌细胞上体内评估了这些杂种的潜在抗肿瘤活性，表现出细胞毒性活性，IC50值在28.8至124.6µM之间。与它们的类似物和前体（VII-X）相比，呋喃和吡唑啉基团的掺入显着增强了抗增殖特性，对两种肿瘤细胞系均无活性。化合物4、5和6对两种细胞系均表现出增强的细胞毒性，而化合物8对HT-29细胞显示出较高的细胞毒活性。分子对接研究揭示了致癌途径相关激酶蛋白的优异自由能值（ΔGbin），我们的计算机数据表明，这些衍生物可能是靶向激酶途径的有前途的化学治疗剂。在所有合成的PIBHQ化合物中，衍生物7和8表现出最好的药物相似特性，值分别为0.53和0.83。ADME结果共同表明，这些化合物中的大多数有望作为临床前测定的潜在候选者。
