Abstract：
The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate for this therapeutic failure.
The current study demonstrated whether N-protected and deprotected amino acid derivatives of 2- aminopyridine could attenuate tumor development using colorectal cancer cell lines.
Biological assays were performed to investigate the anticancer potential of synthesized compounds. The in silico ADME profiling and docking studies were also performed by docking the designed compounds against the active binding site of beta-catenin (CTNNB1) to analyze the binding mode of these compounds. Four derivatives 4a, 4b, 4c, and 4d were selected for investigation of in vitro anticancer potential using colorectal cancer cell line HCT 116. The anti-tumor activities of synthesized compounds were further validated by evaluating the inhibitory effects of these compounds on the target protein beta-catenin through in vitro enzyme inhibitory assay.
The docking analysis revealed favorable binding energies and interactions with the target proteins. The in vitro MTT assay on colorectal cancer cell line HCT 116 and HT29 revealed potential anti-tumor activities with an IC50 range of 3.7-8.1μM and 3.27-7.7 μM, respectively. The inhibitory properties of these compounds on the concentration of beta-catenin by ELISA revealed significant percent inhibition of target protein at 100 μg/ml.
In conclusion, the synthesized compounds showed significant anti-tumor activities both in silico and in vitro, having potential for further investigating its role in colorectal cancer.
The current study demonstrated whether N-protected and deprotected amino acid derivatives of 2- aminopyridine could attenuate tumor development using colorectal cancer cell lines.
Biological assays were performed to investigate the anticancer potential of synthesized compounds. The in silico ADME profiling and docking studies were also performed by docking the designed compounds against the active binding site of beta-catenin (CTNNB1) to analyze the binding mode of these compounds. Four derivatives 4a, 4b, 4c, and 4d were selected for investigation of in vitro anticancer potential using colorectal cancer cell line HCT 116. The anti-tumor activities of synthesized compounds were further validated by evaluating the inhibitory effects of these compounds on the target protein beta-catenin through in vitro enzyme inhibitory assay.
The docking analysis revealed favorable binding energies and interactions with the target proteins. The in vitro MTT assay on colorectal cancer cell line HCT 116 and HT29 revealed potential anti-tumor activities with an IC50 range of 3.7-8.1μM and 3.27-7.7 μM, respectively. The inhibitory properties of these compounds on the concentration of beta-catenin by ELISA revealed significant percent inhibition of target protein at 100 μg/ml.
In conclusion, the synthesized compounds showed significant anti-tumor activities both in silico and in vitro, having potential for further investigating its role in colorectal cancer.
摘要：
对可用的抗癌药物的抗性的发展日益成为主要挑战,并且可以揭示新的化学实体来补偿这种治疗失败。
目前的研究证明了2-氨基吡啶的N-保护和去保护的氨基酸衍生物是否可以使用结直肠癌细胞系来减弱肿瘤的发展。
进行生物测定以研究合成化合物的抗癌潜力。还通过将设计的化合物与β-连环蛋白(CTNNB1)的活性结合位点对接来进行计算机模拟ADME谱分析和对接研究,以分析这些化合物的结合模式。四种衍生物4a，4b,4c,选择4d用于研究使用结直肠癌细胞系HCT116的体外抗癌潜力。通过体外酶抑制试验评价这些化合物对靶蛋白β-catenin的抑制作用,进一步验证了合成化合物的抗肿瘤活性。
对接分析揭示了有利的结合能和与靶蛋白的相互作用。对大肠癌细胞系HCT116和HT29的体外MTT测定显示潜在的抗肿瘤活性，IC50范围为3.7-8.1μM和3.27-7.7μM，分别。通过ELISA,这些化合物对β-连环蛋白浓度的抑制特性揭示了在100μg/ml时靶蛋白的显著抑制百分比。
总之,合成的化合物在计算机和体外均表现出明显的抗肿瘤活性，有可能进一步研究其在结直肠癌中的作用。
目前的研究证明了2-氨基吡啶的N-保护和去保护的氨基酸衍生物是否可以使用结直肠癌细胞系来减弱肿瘤的发展。
进行生物测定以研究合成化合物的抗癌潜力。还通过将设计的化合物与β-连环蛋白(CTNNB1)的活性结合位点对接来进行计算机模拟ADME谱分析和对接研究,以分析这些化合物的结合模式。四种衍生物4a，4b,4c,选择4d用于研究使用结直肠癌细胞系HCT116的体外抗癌潜力。通过体外酶抑制试验评价这些化合物对靶蛋白β-catenin的抑制作用,进一步验证了合成化合物的抗肿瘤活性。
对接分析揭示了有利的结合能和与靶蛋白的相互作用。对大肠癌细胞系HCT116和HT29的体外MTT测定显示潜在的抗肿瘤活性，IC50范围为3.7-8.1μM和3.27-7.7μM，分别。通过ELISA,这些化合物对β-连环蛋白浓度的抑制特性揭示了在100μg/ml时靶蛋白的显著抑制百分比。
总之,合成的化合物在计算机和体外均表现出明显的抗肿瘤活性，有可能进一步研究其在结直肠癌中的作用。
