Hamad Elgazwy Abdel-Sattar S, Soliman Daliah S, Atta-Allah Saad R, Ibrahim Diaa A
Department of Chemistry Faculty of Science, Ain Shams University, Abbassia, 11566, Cairo, Egypt.
Chem Cent J. 2012 May 30;6(1):50. doi: 10.1186/1752-153X-6-50.
In vitro antitumor evaluation of the synthesized 46 compounds of 3,5-diaryl-4,5-dihydropyrazoles against EAC cell lines and 3D QSAR study using pharmacophore and Comparative Molecular Field Analysis (CoMFA) methods were described. CoMFA derived QSAR model shows a good conventional squared correlation coefficient r2 and cross validated correlation coefficient r2cv 0.896 and 0.568 respectively. In this analysis steric and electrostatic field contribute to the QSAR equation by 70% and 30% respectively, suggesting that variation in biological activity of the compounds is dominated by differences in steric (van der Waals) interactions. To visualize the CoMFA steric and electrostatic field from partial least squares (PLS) analysis, contour maps are plotted as percentage contribution to the QSAR equation and are associated with the differences in biological activity.
Pyrazole derivatives exhibit a wide range of biological properties including promising antitumor activity. Furthermore, Aldol condensation assisted organic synthesis has delivered rapid routes to N-containing heterocycles, including pyrazoles. Combining these features, the use of chalconisation-assisted processes will provide rapid access to a targeted dihydropyrazoles library bearing a hydrazino 3D QSAR study using pharmacophore and Comparative Molecular Field Analysis (CoMFA) methods were described for evaluation of antioxidant properties.
Chalcones promoted 1 of the 2 steps in a rapid, convergent synthesis of a small library of hydrazinyl pyrazole derivatives, all of which exhibited significant antitumor activity against Ehrlich Ascites Carcinoma (EAC) human tumor cell line comparable to that of the natural anticancer doxorubicin, as a reference standard during this study. In order to understand the observed pharmacological properties, quantitative structure-activity relationship (3D QSAR) study was initiated.
Chalcones heating provides a rapid and expedient route to a series of pyrazoles to investigate their chracterization scavenging properties. Given their favorable properties, in comparison with known anticancer, these pyrazole derivatives are promising leads for further development and optimization.
描述了合成的46种3,5 - 二芳基 - 4,5 - 二氢吡唑化合物对艾氏腹水癌（EAC）细胞系的体外抗肿瘤评估，以及使用药效团和比较分子场分析（CoMFA）方法进行的3D QSAR研究。CoMFA得出的QSAR模型显示出良好的传统平方相关系数r²和交叉验证相关系数r²cv，分别为0.896和0.568。在此分析中，空间场和静电场对QSAR方程的贡献分别为70%和30%，这表明化合物生物活性的变化主要由空间（范德华）相互作用的差异主导。为了从偏最小二乘法（PLS）分析中可视化CoMFA空间场和静电场，绘制了等高线图，以显示其对QSAR方程的贡献百分比，并与生物活性的差异相关联。
吡唑衍生物具有广泛的生物学特性，包括有前景的抗肿瘤活性。此外，羟醛缩合辅助有机合成提供了通往含氮杂环化合物（包括吡唑）的快速途径。结合这些特点，使用查耳酮化辅助过程将能够快速获得一个靶向的二氢吡唑文库，同时描述了使用药效团和比较分子场分析（CoMFA）方法进行的3D QSAR研究以评估抗氧化性能。
查耳酮促进了肼基吡唑衍生物小文库快速、汇聚合成中的两步反应，所有这些衍生物对艾氏腹水癌（EAC）人肿瘤细胞系均表现出显著的抗肿瘤活性，在本研究中可与天然抗癌药物阿霉素相媲美，作为参考标准。为了理解观察到的药理特性，开展了定量构效关系（3D QSAR）研究。
查耳酮加热为研究一系列吡唑的特性清除性能提供了一条快速便捷的途径。鉴于它们具有良好的特性，与已知抗癌药物相比，这些吡唑衍生物是进一步开发和优化的有前景的先导化合物。
