Copper(ii) l/d-valine-(1,10-phen) complexes target human telomeric G-quadruplex motifs and promote site-specific DNA cleavage and cellular cytotoxicity
| Autor: | Surbhi Sharma, Farukh Arjmand, Sabiha Parveen, Loïc Toupet, Zhen Yu, James A. Cowan |
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| Přispěvatelé: | Aligarh Muslim University, Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Ohio State University [Columbus] (OSU), National Institutes of Health, NIH HL093446United States - India Educational Foundation, USIEFUniversity Grants Committee, UGCOhio State University, OSU, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cleavage rates
Cytotoxic activities Diseases Cellular cytotoxicity 01 natural sciences law.invention First order kinetics chemistry.chemical_compound Coordination Complexes law Electron paramagnetic resonance [PHYS]Physics [physics] Cytotoxins Chemistry Molecular docking simulations Valine Telomere Molecular Docking Simulation Synthesis (chemical) Selectivity Binding affinities Stereochemistry Kinetics Antineoplastic Agents Binding energy 010402 general chemistry Cleavage (embryo) G-quadruplex Article Inorganic Chemistry Time dependent Cell Line Tumor Electron spin resonance spectroscopy Animals Humans MTT assay DNA Cleavage Cell Proliferation Human cancer cells Copper metallography 010405 organic chemistry Copper compounds X ray spectroscopy DNA 0104 chemical sciences G-Quadruplexes Single crystals Cattle Cell culture Drug Screening Assays Antitumor Copper |
| Zdroj: | Dalton Transactions Dalton Transactions, 2020, 49 (28), pp.9888-9899. ⟨10.1039/d0dt01527j⟩ Dalton Transactions, Royal Society of Chemistry, 2020, 49 (28), pp.9888-9899. ⟨10.1039/d0dt01527j⟩ Dalton Trans |
| ISSN: | 1477-9226 1477-9234 |
| Popis: | International audience; Chiral l-/d-valine-(1,10-phen)-Cu(ii) complexes that target G-quadruplex DNA were synthesized and thoroughly characterized by UV-vis, IR, EPR, ESI-MS, elemental analysis and single crystal X-ray spectroscopy. Complexes 1a and 1b crystallized in the monoclinic P21/c and C2 space groups, respectively. On the basis of Wolfe-Shimer analyses, the binding affinities of 1a and 1b with G-quadruplex telomeric DNA were determined, and 1a exhibited significantly higher binding as compared to 1b. Site selective cleavage of G4-DNA was demonstrated by employing the time-dependent PAGE assay, with 1a exhibiting a significantly higher cleavage rate from A1 to G22 (4.32 (±0.13) μM h-1) than 1b (4.29 (±0.11) μM h-1). The DNA cleavage profile demonstrated that both complexes perform non-random double-strand cleavage by following first-order kinetics (kobs = 0.9432 min-1 for 1a and kobs = 0.6574 min-1 for 1b). Molecular docking simulations were performed with both parallel and anti-parallel topologies of the quadruplex to provide a clear insight on G-quadruplex-complex interactions. Complexes 1a and 1b were found to interact strongly at the minor groove cavity of the quadruplex with preferential selectivity for the parallel vs. anti-parallel quadruplex. The cytotoxic activities of complexes 1a and 1b were evaluated on a few notably important human cancer cell lines, viz, breast (MCF-7), pancreatic strains (BxPC3, AsPC1) and liver (Huh7) by an MTT assay. Both 1a and 1b exhibited pronounced cytotoxic activity with remarkably low IC50 values (1-3 μM) for all tested cancer strains. © The Royal Society of Chemistry. |
| Databáze: | OpenAIRE |
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