c -苯杯[4]环氧间苯芳烃化合物在乳腺癌细胞MCF-7中作为药物递送剂的潜力

Dwi Rahmasari Fatmawati, Danny Nur Wahyu Hidayat, Diah Kartika Sari, Rizky Riyami Putri, J. Jumina, Y. S. Kurniawan
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引用次数: 2

摘要

通过常规化疗治疗癌症已被广泛应用;然而,化疗的主要缺点之一是对癌细胞的非选择性靶向,导致各种不良副作用。开发在癌症治疗中更有选择性和更有效的药物递送剂需要进行,以使药物具有治疗效果并将副作用降到最低。在本研究中,化合物C-phenylcalyx[4]间苯二甲酸环氧化物(CFKRE)作为药物递送剂,因为它可以与配体形成宿主复合物相互作用。通过环氧化物的缩合和烷基化两个反应步骤合成了CFKRE化合物。采用FTIR, 1H-和13C-NMR分光光度计分析其结构,然后采用MTT法检测其体外细胞毒性。结果表明,CFKRE收率达70%。CFKRE化合物与PDGFR和EGFR蛋白的分子对接分析显示,与常规化疗药物相比,CFKRE化合物具有较高的结合能。分子动力学研究表明,CFKRE化合物可形成结合能为−350.4 kcal/mol的宿主-配体复合物。CFKRE化合物对MCF-7乳腺癌细胞和Vero细胞的IC50分别为4.04和29.59 μg/mL。这些结果表明,CFKRE化合物是无毒的,有潜力作为新的候选药物递送剂。
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Potential of C-Phenylcalix[4]Resorcinarene Epoxide Compound as Drug Delivery Agent in Breast Cancer Cells MCF-7
Cancer therapy through conventional chemotherapy has been widely applied; however, one of the main disadvantages of chemotherapy is the non-selective targeting of cancer cells which causes various adverse side effects. The development of drug delivery agents that are more selective and effective in cancer therapy needs to be performed so that the drugs have a therapeutic effect and minimize side effects. In this study, the compound C-phenylcalyx[4]resorcinarene epoxide (CFKRE) has acted as a drug delivery agent because it can form host complex interactions with ligands. The CFKRE compound was synthesized through two reaction steps: the condensation and alkylation reactions of the epoxide. The structure was analyzed using FTIR, 1H-, and 13C-NMR spectrophotometers and then tested for in vitro cytotoxicity using the MTT assay. The results showed that 70% yield of CFKRE was obtained. Molecular docking analysis of CFKRE compounds against PDGFR and EGFR proteins showed high binding energy compared to conventional chemotherapeutic agents. Molecular dynamic studies showed that CFKRE compounds could form a host-ligand complex with a −350.4 kcal/mol binding energy. Cytotoxic assay of CFKRE compound against MCF-7 breast cancer cells and Vero cells gave IC50 values of 4.04 and 29.59 μg/mL, respectively. These results indicated that CFKRE compounds are not toxic and have the potential to be utilized as new candidates for drug delivery agents.
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审稿时长
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