{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:35:08Z","timestamp":1788572108536,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of scientific research, King Abdulaziz University","award":["KEP-60-130-38"],"award-info":[{"award-number":["KEP-60-130-38"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>A set of copper(I) coordination compounds with general formula [CuBr(PPh3)(dppz-R)] (dppz-R = dipyrido[3,2-a:2\u2019,3\u2019-c]phenazine (Cu-1), 11-nitrodipyrido[3,2-a:2\u2019,3\u2019-c]phenazine (Cu-2), 11-cyanodipyrido[3,2-a:2\u2019,3\u2019-c]phenazine (Cu-3), dipyrido[3,2-a:2\u2019,3\u2019-c]phenazine-11-phenone (Cu-4), 11,12-dimethyldipyrido[3,2-a:2\u2019,3\u2019-c]phenazine (Cu-5)) have been prepared and characterized by elemental analysis, 1H-NMR and 31P-NMR spectroscopies as well as mass spectrometry. The structure of Cu-1 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 (Ksv) 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 (Cu-3) has the best anticancer activities.<\/jats:p>","DOI":"10.3390\/pharmaceutics13050764","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T22:31:25Z","timestamp":1621549885000},"page":"764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["DNA-Binding and Cytotoxicity of Copper(I) Complexes Containing Functionalized Dipyridylphenazine Ligands"],"prefix":"10.3390","volume":"13","author":[{"given":"Sammar","family":"Alsaedi","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9364-263X","authenticated-orcid":false,"given":"Bandar A.","family":"Babgi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-4749","authenticated-orcid":false,"given":"Magda H.","family":"Abdellattif","sequence":"additional","affiliation":[{"name":"Chemistry Department, Deanship of Scientific Research, College of Sciences, Taif University, Al-Haweiah, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6812-7495","authenticated-orcid":false,"given":"Muhammad N.","family":"Arshad","sequence":"additional","affiliation":[{"name":"Center of Excellence for Advanced Materials Research (CEAMR), King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-3850","authenticated-orcid":false,"given":"Abdul-Hamid M.","family":"Emwas","sequence":"additional","affiliation":[{"name":"Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Jaremko","sequence":"additional","affiliation":[{"name":"Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4433-6783","authenticated-orcid":false,"given":"Mark G.","family":"Humphrey","sequence":"additional","affiliation":[{"name":"Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7905-3209","authenticated-orcid":false,"given":"Abdullah M.","family":"Asiri","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"},{"name":"Center of Excellence for Advanced Materials Research (CEAMR), King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-167X","authenticated-orcid":false,"given":"Mostafa A.","family":"Hussien","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"},{"name":"Department of Chemistry, Faculty of Science, Port Said University, Port Said 42521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1021\/cr980420v","article-title":"Current Status of Platinum-Based Antitumor Drugs","volume":"99","author":"Wong","year":"1999","journal-title":"Chem. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2174\/092986706776872970","article-title":"Platinum Group Antitumor Chemistry: Design and development of New Anticancer Drugs Complementary to Cisplatin","volume":"13","author":"Kettunen","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ctrv.2006.09.006","article-title":"Molecular mechanisms of resistance and toxicity associated with platinating agents","volume":"33","author":"Rabik","year":"2007","journal-title":"Cancer Treat. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drup.2008.02.002","article-title":"Resistance against novel anticancer metal compounds: Differences and similarities","volume":"11","author":"Heffeter","year":"2008","journal-title":"Drug Resist. Updates"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1038\/s41467-018-06574-7","article-title":"A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy","volume":"9","author":"Yu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jab.2015.03.003","article-title":"Coordination compounds in cancer: Past, present and perspectives","volume":"13","author":"Trudu","year":"2015","journal-title":"J. Appl. Biomed."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mookerjee, A., Basu, J.M., Majumder, S., Chatterjee, S., Panda, G.S., Dutta, P., Pal, S., Mukherjee, P., Efferth, T., and Roy, S. (2006). A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo. BMC Cancer, 6.","DOI":"10.1186\/1471-2407-6-267"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2174\/187152009787313837","article-title":"Copper Complexes as Anticancer Agents","volume":"9","author":"Marzano","year":"2009","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.molstruc.2014.06.079","article-title":"Synthesis, characterization, DNA-binding and cleavage studies of polypyridyl copper(II) complexes","volume":"1075","author":"Gubendran","year":"2014","journal-title":"J. Mol. Struct."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.molstruc.2019.02.005","article-title":"Structural analysis, antimicrobial and cytotoxic studies on new metal(II) complexes containing N2O2 donor Schiff base ligand","volume":"1183","author":"Amali","year":"2019","journal-title":"J. Mol. Struct."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Corona-Motolinia, N.D., Mart\u00ednez-Valencia, B., Noriega, L., S\u00e1nchez-Gayt\u00e1n, B.L., M\u00e9ndez-Rojas, M.A., Melendez, F.J., Castro, M.E., and Gonz\u00e1lez-Vergara, E. (2020). Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment. Molecules, 25.","DOI":"10.3390\/molecules25204679"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1039\/C2MT00174H","article-title":"Copper complexes as therapeutic agents","volume":"4","author":"Duncan","year":"2012","journal-title":"Metallomics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1021\/jm701146c","article-title":"In Vitro Antitumor Activity of the Water Soluble Copper(I) Complexes Bearing the Tris(hydroxymethyl)phosphine Ligand","volume":"51","author":"Marzano","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1582-4934.2011.01292.x","article-title":"A novel copper complex induces paraptosis in colon cancer cells via the activation of ER stress signalling","volume":"16","author":"Gandin","year":"2012","journal-title":"J. Cell Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/s10637-010-9466-7","article-title":"Cytotoxicity in human cancer cells and mitochondrial dysfunction induced by a series of new copper(I) complexes containing tris(2-cyanoethyl)phosphines","volume":"29","author":"Zanella","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.jinorgbio.2011.05.007","article-title":"Free Radicals and Antioxidant Defense in Antitumor Therapy, in Antioxidant Enzyme","volume":"105","author":"Starosta","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5052","DOI":"10.1039\/C5DT04011F","article-title":"Copper(i) complexes with phosphine derived from sparfloxacin. Part II: A first insight into the cytotoxic action mode","volume":"45","author":"Komarnicka","year":"2016","journal-title":"Dalton Trans."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1039\/C7DT03917D","article-title":"Copper(i) complexes with phosphine derived from sparfloxacin. Part III: Multifaceted cell death and preliminary study of liposomal formulation of selected copper(i) complexes","volume":"47","author":"Cierniak","year":"2018","journal-title":"Dalton Trans."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.poly.2018.10.062","article-title":"Synthesis, structures, DNA-binding and anticancer activities of some copper(I)-phosphine complexes","volume":"158","author":"Mashat","year":"2019","journal-title":"Polyhedron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"114847","DOI":"10.1016\/j.poly.2020.114847","article-title":"Synthesis, structures, DNA-binding, cytotoxicity and molecular docking of CuBr(PPh3)(diimine)","volume":"192","author":"Babgi","year":"2020","journal-title":"Polyhedron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4791","DOI":"10.1016\/S0040-4039(01)00888-7","article-title":"Formation of aryl-nitrogen bonds using a soluble copper(I) catalyst","volume":"42","author":"Gujadhur","year":"2001","journal-title":"Tetrahedron Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1071\/CH9701023","article-title":"Derivatives of 1,10-Phenanthroline-5,6-quinone","volume":"23","author":"Dickeson","year":"1970","journal-title":"Aust. J. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1080\/00958970108022645","article-title":"Electronic effects of donors and acceptor substituents on dipyrido(3,2-:2\u2032,3\u2032-c)phenazine (dppz)","volume":"54","author":"Arancibia","year":"2001","journal-title":"J. Coord. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.poly.2014.09.004","article-title":"Synthesis, characterization, spectroscopic and electrochemical studies of donor\u2013acceptor ruthenium(II) polypyridine ligand derivatives with potential NLO applications","volume":"85","author":"Crivelli","year":"2015","journal-title":"Polyhedron"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/aoc.1534","article-title":"Synthesis, characterization and DNA binding and photocleavage studies of [Ru(bpy)2BDPPZ]2+, [Ru(dmb)2BDPPZ]2+ and [Ru(phen)2BDPPZ]2+ complexes and their antimicrobial activity","volume":"23","author":"Kumar","year":"2009","journal-title":"Appl. Organomet. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/ejoc.200500548","article-title":"Synthesis of Amino- and Bis(bromomethyl)-Substitued Bi- and TetradentateN-Heteroaromatic Ligands: Building Blocks for Pyrazino-Functionalized Fullerene Dyads","volume":"2006","author":"Kleineweischede","year":"2006","journal-title":"Eur. J. Org. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1080\/10426507.2012.668985","article-title":"Synthesis and Characterization of New N-(Diphenylphosphino)-Naphthylamine Chalcogenides: X-Ray Structures of (1-NHC10H7)P(Se)Ph2 and Ph2P(S)OP(S)Ph2","volume":"187","author":"Emwas","year":"2012","journal-title":"Phosphorus Sulfur Silicon Relat. Elem."},{"key":"ref_28","unstructured":"(2012). CrysAlis PRO, Agilent Technologies."},{"key":"ref_29","first-page":"3","article-title":"Crystal structure refinement with SHELXL","volume":"C71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1107\/S0021889899006020","article-title":"WinGXsuite for small-molecule single-crystal crystallography","volume":"32","author":"Farrugia","year":"1999","journal-title":"J. Appl. Crystallogr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1107\/S0021889802022112","article-title":"Single-crystal structure validation with the program PLATON","volume":"36","author":"Spek","year":"2003","journal-title":"J. Appl. Crystallogr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1107\/S0021889812029111","article-title":"WinGX and ORTEP for Windows: An update","volume":"45","author":"Farrugia","year":"2012","journal-title":"J. Appl. Crystallogr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1007\/s10895-017-2151-x","article-title":"Analytical Techniques Used to Detect DNA Binding Modes of Ruthenium(II) Complexes with Extended Phenanthroline Ring","volume":"27","author":"Devi","year":"2017","journal-title":"J. Fluoresc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1021\/acs.inorgchem.6b02419","article-title":"Copper(I)\u2013Phosphine Polypyridyl Complexes: Synthesis, Characterization, DNA\/HSA Binding Study, and Antiproliferative Activity","volume":"56","author":"Villarreal","year":"2017","journal-title":"Inorg. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3109\/13880209409083012","article-title":"Antibacterial and Antifungal Activities of Nine Medicinal Plants from Zaire","volume":"32","author":"Muanza","year":"1994","journal-title":"Int. J. Pharmacog."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1021\/np50078a006","article-title":"DNA as an Affinity Probe Useful in the Detection and Isolation of Biologically Active Natural Products","volume":"54","author":"Pezzuto","year":"1991","journal-title":"J. Natur. Prod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","article-title":"New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening","volume":"82","author":"Skehan","year":"1990","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_38","first-page":"9","article-title":"PLATONSQUEEZE: A tool for the calculation of the disordered solvent contribution to the calculated structure factors","volume":"C71","author":"Spek","year":"2015","journal-title":"Acta Crystallogr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1039\/C5DT03346B","article-title":"Synthesis of novel pyridyl containing phospholanes and their polynuclear luminescent copper(i) complexes","volume":"45","author":"Musina","year":"2016","journal-title":"Dalton Trans."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9826","DOI":"10.1039\/c3dt51006a","article-title":"Highly efficient thermally activated fluorescence of a new rigid Cu(I) complex [Cu(dmp)(phanephos)]+","volume":"42","author":"Czerwieniec","year":"2013","journal-title":"Dalton Trans."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"128664","DOI":"10.1016\/j.molstruc.2020.128664","article-title":"DNA\/BSA binding of a new oxovanadium (IV) complex of glycylglycine derivative Schiff base ligand","volume":"1219","author":"Kalantari","year":"2020","journal-title":"J. Mol. Struct."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.dyepig.2015.10.008","article-title":"Studies of the binding interactions of dicationic styrylimidazo[1,2-a]pyridinium dyes with duplex and quadruplex DNA","volume":"125","author":"Mahmoud","year":"2016","journal-title":"Dyes Pigments"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jinorgbio.2005.11.018","article-title":"Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage","volume":"100","author":"Selvakumar","year":"2006","journal-title":"J. Inorg. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1021\/om5011275","article-title":"Monomer\u2013Dimer Divergent Behavior toward DNA in a Half-Sandwich Ruthenium(II) Aqua Complex. Antiproliferative Biphasic Activity","volume":"34","author":"Busto","year":"2015","journal-title":"Organometallics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/cr400135x","article-title":"Advances in Copper Complexes as Anticancer Agents","volume":"114","author":"Santini","year":"2014","journal-title":"Chem. Rev."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/5\/764\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:05:01Z","timestamp":1760162701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/5\/764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["pharmaceutics13050764"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13050764","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,20]]}}}