TY - JOUR
T1 - DNA-Binding Capabilities and Anticancer Activities of Ruthenium(II) Cymene Complexes with (Poly)cyclic Aromatic Diamine Ligands
AU - Alsaeedi, Mona S.
AU - Babgi, Bandar A.
AU - Abdellattif, Magda H.
AU - Jedidi, Abdesslem
AU - Humphrey, Mark G.
AU - Hussien, Mostafa A.
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Ruthenium(II) arene complexes of the general formula [RuCl(η6-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru–Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.
AB - Ruthenium(II) arene complexes of the general formula [RuCl(η6-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru–Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.
KW - DNA-binding
KW - anticancer properties
KW - ruthenium(II) arene
UR - http://www.scopus.com/inward/record.url?scp=85099115735&partnerID=8YFLogxK
U2 - 10.3390/MOLECULES26010076
DO - 10.3390/MOLECULES26010076
M3 - Article
SN - 1420-3049
VL - 26
JO - Molecules
JF - Molecules
IS - 1
M1 - 76
ER -