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Design, Synthesis and Biological Evaluation of Novel Gypsogenin Derivatives as Potential Anticancer and Antimicrobial Agents
Chemistry & Biodiversity ( IF 2.9 ) Pub Date : 2024-04-10 , DOI: 10.1002/cbdv.202400471
Safiye Emirdağ 1 , Nafia Gökce Ulusoy 2 , Mehran Aksel 3
Affiliation  

Natural compounds are important sources for the treatment of chronic disorders such as cancer and microbial infectious disorders. In this research, Gypsogenin and its derivatives (2a‐2f) have been tested against different cancer cell lines (MCF‐7, HeLa, Jurkat and K562 cell lines) and further analyzed for cell proliferation, cell death type, and for act of the mechanism. Cell proliferation was determined by the MTT method and cell death types were analyzed with HO/PI staining. Fibroblast Growth Factor 1 (FGF‐1), Interleukin 1 (IL‐1), Interleukin 6 (IL‐6), and Tumor Necrosis Factor Alpha (TNF‐α), key players in breast cancer development and progression, were determined by Elisa kits. Results showed that compound 2e inhibited the MCF‐7 cell line proliferation with an IC50 value of 0.66±0.17 µM with 93.38% apoptosis rate. Compound 2e also decreased FGF‐1, IL‐1, IL‐6, and TNF‐α levels. Molecular docking studies performed in the binding site of FGFR‐1 indicated that compound 2e formed key hydrogen bonding with Arg627 and Asn568. Besides, compounds 2a‐2f were evaluated for their antimicrobial activities against gram‐negative and gram‐positive bacteria and C. albicans via the microdilution method. Overall, compound 2e stands out as a potential anticancer agent for future studies.

中文翻译:

作为潜在抗癌和抗菌剂的新型绞股蓝衍生物的设计、合成和生物学评价

天然化合物是治疗癌症和微生物感染性疾病等慢性疾病的重要来源。在这项研究中,Gypsogenin 及其衍生物 (2a-2f) 针对不同的癌细胞系(MCF-7、HeLa、Jurkat 和 K562 细胞系)进行了测试,并进一步分析了细胞增殖、细胞死亡类型和作用。机制。 MTT法测定细胞增殖,HO/PI染色分析细胞死亡类型。成纤维细胞生长因子 1 (FGF-1)、白细胞介素 1 (IL-1)、白细胞介素 6 (IL-6) 和肿瘤坏死因子 α (TNF-α) 是乳腺癌发生和进展的关键因素,由 Elisa 测定套件。结果显示,化合物2e抑制MCF-7细胞系增殖,IC50值为0.66±0.17 µM,细胞凋亡率为93.38%。化合物 2e 还降低 FGF-1、IL-1、IL-6 和 TNF-α 水平。在 FGFR-1 结合位点进行的分子对接研究表明,化合物 2e 与 Arg627 和 Asn568 形成了关键的氢键。此外,通过微量稀释法评估了化合物2a-2f对革兰氏阴性菌、革兰氏阳性菌以及白色念珠菌的抗菌活性。总体而言,化合物 2e 作为未来研究的潜在抗癌剂脱颖而出。
更新日期:2024-04-10
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