Design, Synthesis, Docking Studies, and Biological Activity of Novel Analogs of Cyclophosphamide as Potential Anticancer Agents.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current medicinal chemistry Pub Date : 2024-10-04 DOI:10.2174/0109298673332921240920065129

Khodayar Gholivand, Soobieh Alemi Rostami, Marzie Sabaghian, Sanam Sadeghi-Mohammadi, Azam Babaei, Rahime Eshaghi Malekshah, Hossein Naderi-Manesh

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Abstract

Introduction: This study aimed to present the synthesis and characterization of four novel analogs of cyclophosphamide (2, 3, 4, 7) and their related precursors (1, 5, 6) and assess their anticancer activity against breast cancerous (MCF-7) and normal (HUVEC) cells.

Method: Notably, 2-(bis(2-chloroethyl)amino)-1,3,2-diazaphospholidine 2-oxide ((2)) and 2-(bis(2-hydroxyethyl)amino)-1,3,2-diazaphospholidine 2-oxide ((7)) exhibited concentration- dependent cytotoxicity against the MCF-7 cell line, with IC50 values of 8.98 and 28.74 μM, respectively.

Result: Annexin V/PI staining and ROS assays demonstrated reduced cell viability and mitochondrial dysfunction. in silico studies involving DFT-D optimization and Molegro virtual docking against B-DNA dodecamer and STAT3 receptors revealed enhanced interactions for certain compounds compared to cyclophosphamide.

Conclusion: Importantly, the in silico and in vitro results corroborated each other, supporting the potential anticancer efficacy of these novel analogs.

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环磷酰胺新型类似物作为潜在抗癌剂的设计、合成、对接研究和生物活性。

简介：本研究旨在介绍四种新型环磷酰胺类似物（2、3、4、7）及其相关前体（1、5、6）的合成和表征，并评估它们对乳腺癌细胞（MCF-7）和正常细胞（HUVEC）的抗癌活性：方法：2-(双(2-氯乙基)氨基)-1,3,2-二氮磷啶 2-氧化物（(2)）和 2-(双(2-羟乙基)氨基)-1,3,2-二氮磷啶 2-氧化物（(7)）对 MCF-7 细胞株具有浓度依赖性细胞毒性，IC50 值分别为 8.98 和 28.74 μM：结果：Annexin V/PI 染色和 ROS 分析表明细胞活力降低和线粒体功能障碍。针对 B-DNA 十二聚体和 STAT3 受体进行 DFT-D 优化和 Molegro 虚拟对接的硅学研究显示，与环磷酰胺相比，某些化合物的相互作用增强：重要的是，硅学和体外结果相互印证，支持了这些新型类似物的潜在抗癌功效。

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来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.