Biological evaluation of rare earth complexes bearing 1H‐imidazo[4,5‐f]‐1,10‐phenanthroline moiety as promising anticancer chemotherapeutics

• Published in: Applied organometallic chemistry Vol. 32; no. 12
• Main Authors: Liu, Yue, Zhou, Xue‐Quan, Lu, Jing, Li, Si‐Tong, Nie, Yan, Tian, Jin‐Lei, Liu, Xin, Yan, Shi‐Ping
• Format: Journal Article
• Language: English
• Published: Chichester Wiley Subscription Services, Inc 01.12.2018
• Subjects: Apoptosis; Biomolecules; Cancer; Cell cycle; Chemistry; Crystallography; Deoxyribonucleic acid; DNA; DNA cleavage; Fluorescence; induced apoptosis; lanthanide(III) complexes; metallodrugs; Rare earth elements; Serum albumin; X ray spectra
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.4617

Six lanthanide(III) complexes with the 2‐(naphthalen‐1‐yl)‐1H‐imidazo[4,5‐f]‐1,10‐phenanthroline ligand have been synthesized and characterized using X‐ray crystallography. The central Ln(III) center displays a distorted square antiprismatic environment with a N2O6 donor set. To study the reactivity of the complexes with possible biological targets, spectroscopic studies and viscosity experiments were used to research their interactions with calf thymus DNA (CT‐DNA) and bovine serum albumin (BSA), taken as model biomolecules. The six complexes are moderate intercalating agents to CT‐DNA and can quench the intrinsic fluorescence of BSA in a static quenching process. Low IC50 values of these complexes were measured using MTT assays on three human cancer cell lines. One of the complexes could induce apoptosis of BEL‐7404 cancer cells via the extrinsic pathway with high expression of caspase‐8, resulting in caspase‐3 activation. Furthermore, that same complex could significantly suppress BEL‐7404 cell proliferation via induced apoptosis with G2/M phase cell cycle. Six lanthanide(III) complexes with the 2‐(naphthalen‐1‐yl)‐1H‐imidazo[4,5‐f]‐1,10‐phenanthroline ligand have been synthesized and characterized. Low IC50 values of these complexes were measured with three human cancer cell lines. Complex 5 could induce BEL‐7404 cancer cell apoptosis via the extrinsic pathway with high expression of caspase‐8, resulting in caspase‐3 activation. Furthermore, complex 5 could significantly suppress BEL‐7404 cell proliferation via induced apoptosis with G2/M phase cell cycle.