新型的别氧嗪类似物：通过激酶筛选，分子对接和ADME研究增强了设计，合成和抗肿瘤功效
Novel alloxazine analogues: design, synthesis, and antitumour efficacy enhanced by kinase screening, molecular docking, and ADME studies
影响因子:5.40000
分区:医学2区 / 生化与分子生物学2区 药物化学2区
发表日期:2024 Dec
作者:
Doaa Samaha, Sawsan Mahmoud, Mosaad Sayed Mohamed, Rokaia S Abdullah, Nageh A Abou Taleb, Tomohisa Nagamatsu, Hamed I Ali
摘要
这项研究描述了新型的同种嗪类似物的发展是有效的抗肿瘤剂，对肿瘤细胞的选择性增强。在45种新化合物中，有29种针对两种人类肿瘤细胞系的生长抑制活性研究，即人类T细胞急性急性淋巴母细胞性白血病细胞系（CCRF-HSB-2）和人口服表皮类癌细胞系（KB）（KB），以及抗二菌Ara-ceration“ Ara-c”。对肿瘤细胞系（CCRF-HSB-2和KB），化合物9E和10J是其类似物中最高的。相关分析表明，IC50值与自动库克结合能量或计算抑制（KI）之间存在牢固的关系。该研究通过使用Gold 5.2.2，Autodock 4.2和Accelrys Discovery Studio 3.5集成的高级建模工具（SBDD）来研究结构活性关系（SARS）。使用Protox-II和Swiss Adme对有效的抗肿瘤剂进行了有效的抗肿瘤药物，对最有效的同嗪衍生物的物理化学特性，药代动力学，类药物和毒性预测进行了提高的选择性。
Abstract
This study describes the development of novel alloxazine analogues as potent antitumor agents with enhanced selectivity for tumour cells. Twenty-nine out of 45 newly compounds were investigated in vitro for their growth inhibitory activities, against two human tumour cell lines, namely, the human T-cell acute lymphoblastoid leukaemia cell line (CCRF-HSB-2) and human oral epidermoid carcinoma cell line (KB), and the antitumor agent "Ara-C" was used as a positive reference in this investigation. Compounds 9e and 10J were the highest among their analogues, against both tumour cell lines (CCRF-HSB-2 and KB). Correlation analyses demonstrated a strong relationship between the IC50 values and AutoDock binding free energy or calculated inhibition (Ki). The study delves into structure-activity relationships (SARs) through advanced modelling tools integrated with structure-based drug design (SBDD) using GOLD 5.2.2, AutoDock 4.2, and Accelrys Discovery Studio 3.5. Physicochemical properties, pharmacokinetics, drug-likeness, and toxicity predictions of the most potent alloxazine derivatives were conducted using ProTox-II and Swiss ADME for effective antitumor agents with improved selectivity.