Alsaedi Sammar, Babgi Bandar A, Abdellattif Magda H, Arshad Muhammad N, Emwas Abdul-Hamid M, Jaremko Mariusz, Humphrey Mark G, Asiri Abdullah M, Hussien Mostafa A
Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
Chemistry Department, Deanship of Scientific Research, College of Sciences, Taif University, Al-Haweiah, P.O. Box 11099, Taif 21944, Saudi Arabia.
Pharmaceutics. 2021 May 20;13(5):764. doi: 10.3390/pharmaceutics13050764.
A set of copper(I) coordination compounds with general formula [CuBr(PPh)(dppz-R)] (dppz-R = dipyrido[3,2-a:2',3'-c]phenazine (), 11-nitrodipyrido[3,2-a:2',3'-c]phenazine (), 11-cyanodipyrido[3,2-a:2',3'-c]phenazine (), dipyrido[3,2-a:2',3'-c]phenazine-11-phenone (), 11,12-dimethyldipyrido[3,2-a:2',3'-c]phenazine ()) have been prepared and characterized by elemental analysis, H-NMR and P-NMR spectroscopies as well as mass spectrometry. The structure of was confirmed by X-ray crystallography. The effect of incorporating different functional groups on the dppz ligand on the binding into CT-DNA was evaluated by absorption spectroscopy, fluorescence quenching of EtBr-DNA adducts, and viscosity measurements. The functional groups affected the binding modes and hence the strength of binding affinities, as suggested by the changes in the relative viscosity. The differences in the quenching constants (K) obtained from the fluorescence quenching assay highlight the importance of the functional groups in altering the binding sites on the DNA. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA changing with the different functional groups. Evaluation of the anticancer activities of the five copper compounds against two different cancer cell lines (M-14 and MCF-7) indicated the importance of the functional groups on the dppz ligand on the anticancer activities. Among the five copper complexes, the cyano-containing complex () has the best anticancer activities.
已制备出通式为[CuBr(PPh)(dppz-R)]的一组铜（I）配位化合物（dppz-R = 二吡啶并[3,2-a:2',3'-c]吩嗪（）、11-硝基二吡啶并[3,2-a:2',3'-c]吩嗪（）、11-氰基二吡啶并[3,2-a:2',3'-c]吩嗪（）、二吡啶并[3,2-a:2',3'-c]吩嗪-11-苯酮（）、11,12-二甲基二吡啶并[3,2-a:2',3'-c]吩嗪（）），并通过元素分析、氢核磁共振和磷核磁共振光谱以及质谱对其进行了表征。通过X射线晶体学确定了的结构。通过吸收光谱、溴化乙锭-DNA加合物的荧光猝灭以及粘度测量，评估了在dppz配体上引入不同官能团对与CT-DNA结合的影响。如相对粘度的变化所示，官能团影响了结合模式，进而影响了结合亲和力的强度。从荧光猝灭试验获得的猝灭常数（K）的差异突出了官能团在改变DNA上结合位点方面的重要性。分子对接数据支持了DNA结合研究，针对B-DNA的相互作用位点和模式随不同官能团而变化。评估这五种铜化合物对两种不同癌细胞系（M-14和MCF-7）的抗癌活性，表明dppz配体上的官能团对抗癌活性很重要。在这五种铜配合物中，含氰基的配合物（）具有最佳的抗癌活性。
