Rehman Sadia, Ikram Muhammad, Khan Afzal, Khan Adnan, Khan Rizwan, Sinnokrot Mutasem Omar, Puduvalli Vinay K, Jadoon Ayub
Department of Chemistry, Abdul Wali Khan University, Mardan, Pakistan.
Department of Microbiology, Abbotabad University of Science and Technology, Abbotabad, Pakistan.
Cell Biochem Biophys. 2025 Mar;83(1):999-1008. doi: 10.1007/s12013-024-01532-1. Epub 2024 Sep 22.
The most typical primary brain tumor, glioblastoma multiforme (GBM), has a dismal prognosis. They are removed through arduous, potentially fatal operations. The primary cause of tumor recurrence following surgery is glioblastoma stem cells (GSCs). In order to combat the recurrent glioblastoma malignant cells, medications have been developed. Chemotherapies now in use are expensive and encounter resistance. To combat inherent and developed resistance, new and powerful chemotherapeutics are being synthesized. In this regard, dicoumarols were deprotonated by triethylamine to produce corresponding salts which are reported and used for the first time for human antiglioblastoma activity. Spectroscopic characterizations like H and C-NMR were carried out. The cytotoxicity of normal human astrocytes (NHA) and human glioblastoma cells (A172 and LN229) were both examined in terms of dose and time dependence. The range of the IC value for all the deprotonated derivatives against A172 was found to be 2.81-0.24 µM, whereas the range against LN229 was found to be 2.50-0.85 µM. According to cytotoxicity results, malignant cell death was seen in GBM cells treated with triethylamine salts of dicoumarols compared to the control group, which suggested that salts may cause apoptosis in GBM cells. Antimicrobial and antifungal activities were also investigated for all the triethylamine salts of dicoumarols suggesting that salt formation enhances antimicrobial potentials manyfolds compared to the standard drug used. Free radical activities were also investigated using DPPH free radicals.
最典型的原发性脑肿瘤——多形性胶质母细胞瘤（GBM），预后很差。它们通过艰巨且可能致命的手术切除。手术后肿瘤复发的主要原因是胶质母细胞瘤干细胞（GSCs）。为了对抗复发性胶质母细胞瘤恶性细胞，已研发出药物。目前使用的化疗药物价格昂贵且会产生耐药性。为了对抗内在的和产生的耐药性，正在合成新型强效化疗药物。在这方面，香豆素双香豆素被三乙胺去质子化以生成相应的盐，这些盐首次被报道并用于人类抗胶质母细胞瘤活性研究。进行了诸如氢核磁共振和碳核磁共振等光谱表征。从剂量和时间依赖性方面研究了正常人星形胶质细胞（NHA）以及人胶质母细胞瘤细胞（A172和LN229）的细胞毒性。发现所有去质子化衍生物对A172的半数抑制浓度（IC）值范围为2.81 - 0.24微摩尔，而对LN229的范围为2.50 - 0.85微摩尔。根据细胞毒性结果，与对照组相比，用香豆素双香豆素三乙胺盐处理的GBM细胞出现恶性细胞死亡，这表明这些盐可能导致GBM细胞凋亡。还研究了香豆素双香豆素所有三乙胺盐的抗菌和抗真菌活性，结果表明与使用的标准药物相比，盐的形成使抗菌潜力提高了许多倍。还使用二苯基苦味酰基自由基（DPPH）研究了自由基活性。
