Synthesis, characterization, in vitro cytotoxicity and DNA interaction study of phosphanegold(I) complexes with dithiocarbamate ligands

被引:31
作者
Al-Jaroudi, Said S. [1 ]
Altaf, Muhammad [2 ]
Seliman, Adam A. [1 ]
Yadav, Shipra [3 ]
Arjmand, Farukh [3 ]
Alhoshani, Ali [4 ]
Korashy, Hesham M. [4 ]
Ahmad, Saeed [5 ]
Isab, Anvarhusein A. [1 ]
机构
[1] King Fahd Univ Petr & Minerals, Dept Chem, Dhahran 31261, Saudi Arabia
[2] King Fahd Univ Petr & Minerals, Ctr Res Excellence Nanotechnol, Dhahran 31261, Saudi Arabia
[3] Aligarh Muslim Univ, Dept Chem, Aligarh 202002, Uttar Pradesh, India
[4] King Saud Univ, Coll Pharm, Pharmacol & Toxicol Dept, Riyadh 11451, Saudi Arabia
[5] Prince Sattam bin Abdulaziz Univ, Coll Sci & Humanities, Dept Chem, Al Kharj 11942, Saudi Arabia
关键词
Phosphine Au(I) complexes; Dithiocarbamates; Anticancer; CT-DNA binding studies; Mononucleotide interaction and molecular docking; EFFECTIVE CORE POTENTIALS; ANTICANCER ACTIVITY; MOLECULAR CALCULATIONS; GOLD(III) COMPLEXES; CARBENE COMPLEXES; DRUG; FLUORESCENCE; DERIVATIVES; BEHAVIOR; DENSITY;
D O I
10.1016/j.ica.2017.04.040
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
A new series of phosphanegold(I) dithiocarbamate complexes with general formula [AU(PR3)(S2CNR'(2))], 1-5 (Where R= Methyl, ethyl, isopropyl and R' = Methyl, ethyl) were synthesized and characterized by elemental analysis, FTIR and multinuclear NMR spectroscopy. The molecular structure of one of them, [Au(PMe3)(S2CNMe2)] (1) was determined by single crystal X-ray crystallography, which revealed linear geometry around the Au(I) metal center. The in vitro cytotoxicity of all Au(I) complexes was studied against two human cancer cell lines, A549 and HepG2. All the complexes showed significantly higher potency (4 to 6-fold for A549 and 3 to 5-fold for HepG2 cell line) than the commercial chemotherapeutic drug, cisplatin. The in vitro DNA binding abilities of Au(I) complexes 1-5 were examined by employing different biophysical techniques, viz, UV-Vis titrations, fluorescence spectroscopy and circular dichroism. The UV-Vis titration of Au(I) complexes with Cl' DNA revealed that the complexes bound to CT DNA via electrostatic interactions, and the intrinsic binding constant (1(b) values for 1-5 were found to be 3.90 x 10(4), 4.74 x 10(4), 6.81 x 10(4), 8.53 x 10(4) and 2.48 x 10(4)M(-1) respectively, which suggested the highest binding propensity for complex 4. In addition, molecular docking studies of the Au(I) complexes were performed with B-DNA to visualize the preferential docking position, and the results showed the binding of complexes to the adenine-thymine residues in the minor groove of the DNA. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:37 / 48
页数:12
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