Abstract

Chromene and its derivatives are generally spread in nature. Heterocylic-based compounds like chromenes have displayed pharmacological activities. Chromene derivatives are critical due to some biological features such as anticancer activity. CML, chronic myelogenous leukemia, is a fatal malignancy determined by resistance to apoptosis and contains the Philadelphia chromosome. Induction of apoptosis is one of the main approaches in cancer therapy. In this research, benzochromene derivative, 2-amino-4-(4-methoxy phenyl)-4H-benzochromene-3-carbonitrile (4-MC) was tested for cytotoxic and apoptotic induction activities in the human leukemic K562 cell line. The MTT growth inhibition assay was used to determine the cellular growth and survival. Moreover, the binding attribute of 4-MC with double helix DNA was assessed by some spectroscopic and viscosity measurement, and also for docking analysis. 4-MC exhibited good cytotoxicity on K562 cell line and the IC₅₀ value was calculated to be 30 µM. Furthermore, the mechanisms of apoptosis induction were determined morphologically by fluorescence dual staining with acridine orange and ethidium bromide and cell cycle analysis was based on DNA content, as well as the presence of phosphatidyl serine on the outside of the cells by the flow cytometric method. The results showed that 4-MC had potent cytotoxic activity via sub-G1 cell cycle arrest and induction of apoptosis. The experimental and simulation studies reported that 4-MC binds to ctDNA through groove binding mode with the binding constant (K_b) of 2.5 × 10³ M⁻¹. These data represent a considerable anticancer potential of 4-MC and could be suggested for further pharmacological studies.

 抽象的

苯并呋喃及其衍生物普遍分布在自然界中。色烯等杂环化合物已显示出药理活性。色烯衍生物由于某些生物学特性（例如抗癌活性）而至关重要。 CML，即慢性粒细胞白血病，是一种由细胞凋亡抵抗决定的致命恶性肿瘤，含有费城染色体。诱导细胞凋亡是癌症治疗的主要方法之一。在本研究中，测试了苯并色烯衍生物 2-氨基-4-(4-甲氧基苯基)-4 H-苯并色烯-3-甲腈 (4-MC) 在人白血病 K562 细胞系中的细胞毒性和细胞凋亡诱导活性。 MTT生长抑制测定用于测定细胞生长和存活。此外，通过一些光谱和粘度测量以及对接分析来评估4-MC与双螺旋DNA的结合属性。 4-MC对K562细胞系表现出良好的细胞毒性，计算IC ₅₀值为30 µM。此外，通过吖啶橙和溴化乙锭的荧光双重染色从形态学上确定细胞凋亡诱导的机制，并基于DNA含量以及通过流式细胞术方法检测细胞外部磷脂酰丝氨酸的存在进行细胞周期分析。结果表明，4-MC通过亚 G1 细胞周期阻滞和诱导细胞凋亡而具有有效的细胞毒活性。实验和模拟研究表明4-MC通过凹槽结合模式与ctDNA结合，结合常数( K _b )为2.5 × 10 ³ M ^-1 。 这些数据代表了 4-MC 相当大的抗癌潜力，可用于进一步的药理学研究。