Maia Ana, Ventura Cathy, Santos Adriana O, Nunes Maria J, Boto Renato E F, Sousa Ângela, Silvestre Samuel M, Almeida Paulo, Serrano João L
CICS-UBI-Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilhã, Portugal.
Department of Chemistry, University of Beira Interior, Rua Marquês de Ávila e Bolama, 6201-001 Covilhã, Portugal.
Molecules. 2024 Nov 26;29(23):5581. doi: 10.3390/molecules29235581.
Cancer treatment remains a significant challenge, with chemotherapy still being one of the most common therapeutic approaches. Based on our initial studies of symmetric monomethine cyanine dyes, which showed potential against colorectal cancer, this study explored several asymmetric cyanines, aiming to develop more potent and selective antitumor agents, particularly against colorectal cancer. In pursuit of this goal, we have designed, synthesized, and structurally characterized twelve new cyanine dyes. Their antiproliferative effects were then investigated in vitro against both tumor and non-tumor cell lines. Notably, the two most promising dyes in terms of potency and selectivity against Caco-2 colorectal cancer cells were derived from the combination of -methylbenzoxazole and -methylquinoline (dye ), as well as -ethylbenzothiazole and -ethyl-6-nitrobenzothiazole (dye ). The potential mechanisms behind their antiproliferative action were also explored, revealing that both dyes penetrate cells and localize within the cytoplasm and nucleus. Furthermore, dye was found to slightly induce apoptosis without causing significant cell cycle arrest, in contrast to dye , which increased the number of cells in the G0/G1 phase. Interestingly, both dyes exhibited marked topoisomerase II inhibitory effects, particularly cyanine , which may further explain their antiproliferative activity. Additionally, drug-likeness properties were predicted for both dyes. Overall, cyanine emerged as the most promising candidate for further investigation as a potential treatment for colorectal cancer.
癌症治疗仍然是一项重大挑战，化疗仍是最常见的治疗方法之一。基于我们对对称单甲川花菁染料的初步研究，该研究显示出对结直肠癌的治疗潜力，本研究探索了几种不对称花菁，旨在开发更有效、更具选择性的抗肿瘤药物，尤其是针对结直肠癌的药物。为了实现这一目标，我们设计、合成并对12种新型花菁染料进行了结构表征。然后在体外研究了它们对肿瘤细胞系和非肿瘤细胞系的抗增殖作用。值得注意的是，就对Caco-2结直肠癌细胞的效力和选择性而言，两种最有前景的染料分别来自于 - 甲基苯并恶唑和 - 甲基喹啉的组合（染料 ），以及 - 乙基苯并噻唑和 - 乙基 - 6 - 硝基苯并噻唑（染料 ）。我们还探索了它们抗增殖作用背后的潜在机制，发现这两种染料都能穿透细胞并定位在细胞质和细胞核内。此外，与染料 相比，染料 被发现能轻微诱导细胞凋亡而不会导致明显的细胞周期停滞，染料 增加了处于G0/G1期的细胞数量。有趣的是，两种染料都表现出显著的拓扑异构酶II抑制作用，尤其是花菁 ，这可能进一步解释了它们的抗增殖活性。此外，还预测了两种染料的类药性质。总体而言，花菁 作为结直肠癌潜在治疗药物的进一步研究中成为最有前景的候选药物。
