Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 23732223, Chile.
Molecules. 2023 Oct 19;28(20):7172. doi: 10.3390/molecules28207172.
Based on previous results with benzoindazolequinone (BIZQ) and 3-methylnaphtho [2,3-d]isoxazole-4,9-quinone (NIQ) derivatives, a novel series of chalcone-1,4-naphthoquinone/benzohydroquinone (CNQ and CBHQ) compounds were synthesized from 2-acetyl-5,8-dihydro-6-(4-methyl-3-pentenyl)-1,4-naphthohydroquinone. Their structures were elucidated via spectroscopy. These hybrids were assessed in vivo for their antiproliferative activity on MCF-7 breast adenocarcinoma and HT-29 colorectal carcinoma cells, revealing cytotoxicity with IC values between 6.0 and 110.5 µM. CBHQ hybrids and displayed enhanced cytotoxicity against both cell lines, whereas CNQ hybrids - and exhibited higher cytotoxic activity against MCF-7 cells. Docking studies showed strong binding energies (ΔG) of CNQs to kinase proteins involved in carcinogenic pathways. Furthermore, our in silico analysis of drug absorption, distribution, metabolism, and excretion (ADME) properties suggests their potential as candidates for cancer pre-clinical assays.
基于苯并吲唑醌（BIZQ）和 3-甲基萘并[2,3-d]异恶唑-4,9-醌（NIQ）衍生物的先前结果，我们从 2-乙酰基-5,8-二氢-6-（4-甲基-3-戊烯基）-1,4-萘二氢醌合成了一系列新型查尔酮-1,4-萘醌/苯并氢醌（CNQ 和 CBHQ）化合物。通过光谱法阐明了它们的结构。这些杂种在体内对 MCF-7 乳腺癌和 HT-29 结肠直肠癌细胞的增殖活性进行了评估，显示出 IC 值在 6.0 到 110.5 µM 之间的细胞毒性。CBHQ 杂种 和 对两种细胞系均显示出增强的细胞毒性，而 CNQ 杂种 - 和 对 MCF-7 细胞表现出更高的细胞毒性。对接研究表明，CNQs 与致癌途径中涉及的激酶蛋白具有很强的结合能（ΔG）。此外，我们对药物吸收、分布、代谢和排泄（ADME）特性的计算机分析表明，它们有可能成为癌症临床前试验的候选药物。
