Department of Chemistry, Faculty of Arts & Science, Yildiz Technical University, Istanbul, Turkey.
Department of Biomedical Engineering, Faculty of Engineering and Architecture, Istanbul Arel University, Istanbul, Turkey.
Nanotechnology. 2024 May 7;35(30). doi: 10.1088/1361-6528/ad403e.
Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compoundwhich was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative. This coumarin derivativeloaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, -16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained-loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV-vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. Therelease offrom the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively.-loaded PLGA nanoparticles displayed remarkably effective anticancer activity than. The IC50 values were determined as IC(-loaded PLGA nanoparticles): 0.42 ± 0.01 mg mland IC(freemolecule): 5.74 ± 3.82 mg mlagainst MCF-7 cells, and as IC(-loaded PLGA nanoparticles): 0.77 ± 0.12 mg mland IC(freemolecule): 1.32 ± 0.31 mg mlagainst HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release.
尽管在上个世纪发现了许多阻止不受控制的细胞分裂过程的化疗药物，但仍有许多研究致力于开发具有更高抗癌疗效和更低副作用水平的药物。在这里，我们设计、合成并表征了六种新型香豆素-三唑杂合体，并评估了对乳腺癌细胞系 MCF-7 和人宫颈癌细胞系人宫颈癌腺癌细胞系（HeLa）具有最高潜力的一种的抗癌活性。具有最低 IC50 值的包含苯基取代基的香豆素衍生物化合物对所研究的癌细胞系显示出最高的细胞毒性。此外，通过乳化溶剂蒸发法制备的聚（乳酸-共-羟基乙酸）纳米粒子（PLGA NPs）作为药物递送系统平台的潜在用途在选定的香豆素衍生物上进行了研究。该香豆素衍生物负载的 PLGA NPs 的平均粒径为 225.90 ± 2.96 nm，-16.90 ± 0.85 mV ζ 电位和 4.12 ± 0.90%的载药量。通过傅里叶变换红外光谱（FT-IR）、紫外-可见光谱、扫描电子显微镜以及热重分析、拉曼和 X 射线衍射对所获得的负载 PLGA 纳米粒子进行了光谱和微观分析。在初始 6 小时内突释后，纳米粒子的释放呈现出持续释放的控制释放曲线，此外，在 pH 值为 7.4 和 5.5 时，分别获得了 50%和 85%的总释放率。负载 PLGA 纳米粒子的抗癌活性明显优于游离药物分子。在孵育 24 小时后，对 MCF-7 细胞的 IC50 值分别为 IC（负载 PLGA 纳米粒子）：0.42 ± 0.01 mg/ml 和 IC（游离分子）：5.74 ± 3.82 mg/ml，对 HeLa 细胞的 IC50 值分别为 IC（负载 PLGA 纳米粒子）：0.77 ± 0.12 mg/ml 和 IC（游离分子）：1.32 ± 0.31 mg/ml。我们的研究结果表明，三唑取代的香豆素可以通过整合到聚合物药物递送系统中作为抗癌药物使用，从而提高药物载药量并有效控制药物释放。
