Topo I inhibition, DNA photocleavage, Molecular docking and cytotoxicities of two new phenanthroline‐based ruthenium complexes

Abstract

Two ruthenium complexes containing a new phenanthroline‐based ligand pai (pai = 2‐(5‐(1, 10‐ phenanthroline))‐1H‐acenaphtho[1′,2′:4,5]imidazole) were synthesized and characterized. Two ruthenium complexes were found to cleave DNA under irradiation, interact with CT‐DNA by intercalation. Furthermore, DNA topoisomerase inhibition experiments indicated that complex 2 exhibited higher topoisomerase I inhibition activity (IC50 = 10 μM) than complex 1 (IC50 = 40 μM). Molecular modeling studies revealed that complex 2 stabilized Top1cc complex via π‐π interaction and the formation of hydrogen bond. The cytotoxicity of complexes 1 and 2 against Eca‐109 and A549 cells was also evaluate by MTT method, indicating that complex 2 exhibited good anticancer activity against Eca‐109 cells (IC50 = 17.23 ± 0.22 μM), but two ruthenium complexes displayed weak anticancer activity against A549 cells.

Fifty Shades of Phenanthroline: Synthesis Strategies to Functionalize 1,10-Phenanthroline in All Positions

“…The reactivity of the CHO group has been exploited in a few cases ( e.g. , formation of imine bonds with rhodamine and synthesis of benzimidazoles with diketones or diamines). 903 can be further oxidized into 899 through a Pinnick reaction (Scheme ) instead of the more conventional method (HNO 3 at reflux).…”

An Overview of the Potential Medicinal and Pharmaceutical Properties of Ru(II)/(III) Complexes

“…A number of studies included subsequent molecular docking DFT calculations to further investigate the interactions of ruthenium complex-drug target systems and to obtain reliable estimates of binding energies and binding sites. Examples of such a protocol include half-sandwich ruthenium(II) complexes with human serum albumin (HSA) [131]; nitrosyl ruthenium(II) complex with bovine serum albumin (BSA) [132]; Ru(II)-arene complexes with DNA and BSA [115]; ruthenium(II) polypyridyl complexes with β-amyloid peptide [19] and DNA [133,134] cyclopentadienyl-; cyclooctaniedyl-based ruthenium(II) and anastrozole-, and letrozole-based ruthenium(III) complexes with human aromatase [135]; Ru(III) chelated with (E)-2-((phenylamino)-N-(pyridine-2-yl)methylene)acetohydrazide ligand bound to lanes-terol 14 alpha-demetyhlase (CYP51) enzyme of E. coli as a candidate for an antibacterial and antioxidative agent [136], a dinuclear Ru(II) complex; [(Ru(phen) 2 ) 2 -(tpphz)] 4+ (where phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) with G-actin monomers to block its transformation to F-actin filaments [137]; ruthenium(II) containing phenazine (or phenanthroline) rings intercalating the DNA (and also as DNA "light switches" [138]) and bound to DNA topoisomerase I [139,140]; novel Ru(II)-arene complexes with non-steroidal antiinflammatory drugs bounded to the COX-2 enzyme [141,142], as well as HSA and DNA [143]; photoreactive Ru(II) complexes with telomeric G-Quadruplex DNA [144]; Ru(II)-Schiff base complexes inhibiting HepG2 cells [145]; ruthenium(II)-bipyridine-calixarene complex with BSA and ovalbumin [146]; and ruthenium(II)-purine complexes with BSA [122]. A number of studies included subsequent molecular docking DFT calculations to fur ther investigate the interactions of ruthenium complex-drug target systems and to obtain reliable estimates of binding energies and binding sites.…”

Synthesis, anticancer evaluation and molecular docking studies of new benzimidazole- 1,3,4-oxadiazole derivatives as human topoisomerase types I poison

“…In the field of anticancer drugs, DNA topoisomerase I has been reported to be an important target for anticancer agents but topoisomerase inhibitors have several barriers and limitations. These include poor solubility, accumulation in target tissues or organs and prolonged half-life in plasma as well as drug efflux from the target cells and cancer cell resistance [14][15][16][17] .…”