喹唑啉-4(1H)-单链香豆素作为强效抗癌剂的体外细胞毒性和机理研究

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Dinesh Singla, Palak Sharma, Vijay Luxami, Kamaldeep Paul
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引用次数: 0

摘要

通过后期功能化方法合成的喹唑啉酮-香豆素共轭物对代表九种不同癌症类型的 60 种人类癌细胞系进行了体外生物活性评估。在合成的化合物中,有 8 种化合物在各种癌症类型中显示出显著的生长抑制活性,其中化合物 23 的细胞毒性尤为突出。进一步的研究涉及化合物 23 对 NCI-60 癌细胞株进行的五剂量试验,结果显示了其在不同浓度下的疗效。此外,结合研究还阐明了它与人血清白蛋白(HSA)和 DNA 的相互作用。结果表明,23 与 HSA 有很强的结合亲和力,其结合常数高达 2.26 × 105 M-1。此外,它与 DNA 的相互作用是通过插层实现的,特别是在 DNA 链的碱基对之间,结合常数为 5.51 × 104 M-1。这表明化合物 23 既能与 DNA 结合,也能与转运蛋白结合,是一种具有潜在治疗应用前景的药源体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

In Vitro Cytotoxicity and Mechanistic Investigation of Quinazolin-4(1H)-One Linked Coumarin as a Potent Anticancer Agent

In Vitro Cytotoxicity and Mechanistic Investigation of Quinazolin-4(1H)-One Linked Coumarin as a Potent Anticancer Agent

Quinazolinone-coumarin conjugates synthesized through Late-Stage Functionalization approach are evaluated for their in vitro biological activity for 60 human cancer cell lines representing nine different cancer types. Among the synthesized compounds, eight displayed significant growth inhibitory activity across a spectrum of cancer types, with compound 23 demonstrating particularly notable cytotoxicity. Further investigation involved a five-dose assay of compound 23 against NCI-60 cancer cell lines, revealing its efficacy at different concentrations. Additionally, binding studies elucidated its interaction with Human Serum Albumin (HSA) and DNA. The results indicated a strong binding affinity of 23 with HSA, evidenced by a high binding constant (2.26 × 105 M−1). Moreover, its interaction with DNA occurred via intercalation, specifically between the base pairs of DNA strands, with a binding constant of 5.51 × 104 M−1. This suggests that compound 23 has the ability to bind to both DNA and transport proteins, making it a promising pharmacophore with potential therapeutic applications.

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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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