摘要
背景: 6-氟-3-(4H-1,2,4-三唑-3-基)喹啉-4(1H)-酮是有前途的抗肿瘤药物,具有大量关于其对人类癌细胞系的深远细胞毒性作用的数据。 目的: 我们试图使用计算机辅助多元回归分析对一系列先前报道的氟喹诺酮类类似物进行定量结构细胞毒性关系(QSCR)分析,并研究这些同源物之间的细胞毒性诱导结构参数。 方法:采用Vlife MDS 4.6软件中嵌入的随机选择方法,将数据集分离为6-氟-3-(4H-1,2,4-三唑-3-基)喹啉-4(1H)-1的训练组和试验组,并进行QSCR分析。接下来,对生成的QSCR模型进行交叉验证以及外部测试集预测。最后,利用MinitabR软件对数据进行分析并形成等值线图,以推断这些同源物之间的细胞毒性诱导结构参数。 结果:经过验证的QSCR模型表现出92.27%的统计显着预测值。我们的QSCR模型揭示了氢计数与细胞毒性之间的直接比例,以及硫和氮的排除,以及未来潜在的6-氟-3-(4H-1,2,4-三唑-3-基)喹啉-4(1H)-酮类似物中环的拥挤较小。基于QSCR模型预测和轮廓图分析,从头REPUBLIC1986分子对CHO细胞系的预测IC50(μM)为0.45,并且适合于抗卵巢癌活性所必需的盐的形成。 结论:所开发的QSCR模型在设计新型、强效、更安全的抗癌药物时具有相关性,以6-氟-3-(4H-1,2,4-三唑-3-基)喹啉-4(1H)-酮为种子化合物。
关键词: 6-氟-3-(4H-1,2,4-三唑-3-基)喹啉-4(1H)-酮,中国仓鼠卵巢细胞系,卵巢癌,计算机辅助多元回归分析,定量结构细胞毒性关系(QSCR),轮廓图。
Current Medicinal Chemistry
Title:QSCR Analysis of Cytotoxicity of 6-Fluoro-3-(4H-1,2,4-triazol-3- yl)quinolin-4(1H)-ones on Chinese Hamster Ovary Cell Line: Design of REPUBLIC1986
Volume: 29 Issue: 2
关键词: 6-氟-3-(4H-1,2,4-三唑-3-基)喹啉-4(1H)-酮,中国仓鼠卵巢细胞系,卵巢癌,计算机辅助多元回归分析,定量结构细胞毒性关系(QSCR),轮廓图。
摘要: Background: 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-ones are promising antitumor agents with enormous data on their profound cytotoxic effects on the human cancer cell lines.
Objectives: We sought to perform a Quantitative structure cytotoxicity relationship (QSCR) analysis of a series of previously reported fluoroquinolone analogues using computerassisted multiple regression analysis and investigate the cytotoxicity-inducing structural parameters among these congeners.
Methods: The dataset was segregated into training and test sets of 6-Fluoro-3-(4H-1,2,4- triazol-3-yl)quinolin-4(1H)-ones by using a random selection method embedded in Vlife MDS 4.6 software and subjected to QSCR analysis. Next, cross-validation of the generated QSCR models was performed along with the external test set prediction. Finally, the data was analyzed and contour plots were developed to deduce the cytotoxicity-inducing structural parameters among these congeners using Minitab® software.
Results: The validated QSCR model exhibited a statistically significant predictive value of 92.27 percent. Our QSCR model revealed a direct proportionality between hydrogen counts and cytotoxicity, and exclusion of sulphur and nitrogen with lesser crowding of cyclopropyl rings in future potential 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-one analogues. Based on the QSCR model predictions and contour plot analysis, the de novo REPUBLIC1986 molecule provided the best hit with predicted IC50 (μM) of 0.45 against CHO cell line and is amenable to salt formation crucial for anti-ovarian cancer activity.
Conclusion: These findings suggest the relevancy of the developed QSCR model in designing novel, potent, and safer anti-cancer drugs with 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin- 4(1H)-ones as seed compounds.
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QSCR Analysis of Cytotoxicity of 6-Fluoro-3-(4H-1,2,4-triazol-3- yl)quinolin-4(1H)-ones on Chinese Hamster Ovary Cell Line: Design of REPUBLIC1986, Current Medicinal Chemistry 2022; 29 (2) . https://dx.doi.org/10.2174/0929867328666210623150552
DOI https://dx.doi.org/10.2174/0929867328666210623150552 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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