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Updated: Jul 13, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

Published on: February 9, 2021

合成,抗癌活性,以及在体研究中对5 - - 3 - 基) - - - N - - -4 - - H - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Mohamed Jawed Ahsan¹, Krishna Gautam¹, Amena Ali²

¹Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur 302039, Rajasthan, India.

Molecules (Basel, Switzerland)

|October 14, 2023

概括

合成了10种新的三胺类类似物,并对抗癌活性进行了测试. 化合物4i对多种癌细胞系表现出有前途的活性,具有潜在的蛋白抑制和有利的ADME/毒性概况.

科学领域:

药用化学医学化学
有机合成有机合成
药理学药理学是指药理学的学科.

背景情况:

新型抗癌药物的开发对于改善癌症治疗结果至关重要.
三胺衍生物已经显示出作为治疗剂的潜力.
鉴定具有强大和选择性的抗癌活性的新化合物仍然是一个重大挑战.

研究的目的:

为了合成和表征新型的5-(3-甲基) -N--4H-1,2,4-三醇-3-胺类同类物.
为了评估这些化合物的体外抗癌活性与人类癌症细胞系的小组相比.
研究分子相互作用并预测合成化合物的药理动力学和毒理学概况.

主要方法:

通过三步程序合成十种5-(3-甲) -N--4H-1,2,4-三醇-3-胺类型 (4a-j) 的类似物.
使用美国国家癌症研究所 (NCI US) 协议对58个癌细胞系进行10−5M的抗癌活性查.
分子对接研究的目标是氨酸-combretastatin A-4结合部位 (PDB ID: 5LYJ).
使用瑞士ADME和ProTox-II软件进行ADME (吸收,分布,新陈代谢,分泌) 和毒性预测.

主要成果:

化合物4a-j已成功合成和表征.
几种化合物表现出显著的抗癌活性,其中化合物4e对SNB-75 (中枢神经系统癌症) 显示41.25%的生长抑制.
化合物4i在多个细胞系中显示出有希望的平均生长抑制,包括SNB-75 (38.94% PGI),UO-31 (30.14% PGI),CCRF-CEM (26.92% PGI),EKVX (26.61% PGI) 和OVCAR-5 (23.12% PGI).
分子对接揭示了有效的结合亲和力 (-6.502到-8.341千卡/mol) 到素结合部位,与化合物4i显示一个结合亲和力 -8.149千卡/mol,并形成一个H键与Asn258.8.
ADME预测表明没有违反利宾斯基五项规则,毒性预测表明LD50在440-500毫克/公斤之间 (第四类毒性).

结论:

合成的5-(3-甲基) -N--4H-1,2,4-三醇-3-胺类同类物具有显著的抗癌潜力.
化合物4i是进一步抗癌药物开发的有希望的主要候选者,特别是由于它对各种癌症细胞系的活性和有利的预测特性.
这些发现支持氨酸抑制作为一种潜在的作用机制,并需要进一步的体内研究.

关键词:

在ADME研究中,研究人员研究了ADME的研究.这是一种抗癌药物.细胞系细胞系的细胞系.分子对接的分子对接.三醇三醇的使用方法管道中的管道.

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