Evaluation of cytotoxic potential of structurally well-characterized RNA targeted ionic non-steroidal anti-inflammatory (NSAID) Cu(ii) & Zn(ii) DACH–mefenamato drug conjugates against human cancer cell lines

摘要

New RNA targeted ionic [Cu(DACH) _(2) (H _(2) O) _(2) ](mef) _(2) , 1 and [Zn(DACH) _(2) (H _(2) O) _(2) ](mef) _(2) , 2 drug conjugates were synthesized and characterized by spectroscopic techniques FT-IR, UV-vis, EPR in case of 1 and ~(1) H and ~(13) C NMR in case of 2 , ESI-MS, thermogravimetric analysis and single-crystal X-ray structure determination in case of 1 . The interaction studies of 1 & 2 with most likely drug targets like ctDNA and tRNA were performed which demonstrated that the complexes 1 and 2 exhibited strong preferential binding to tRNA as compared to ctDNA, K _(b) = 2.52(±0.04) × 10 ~(5) M ~(?1) , 7.85(±0.02) × 10 ~(4) M ~(?1) , respectively. Scanning electron microscopy analyses of complex-ctDNA/tRNA condensates suggested the interaction of complexes with ctDNA/tRNA had occurred, followed by lengthening of DNA double helix and bulge region of tRNA. Cytotoxic activity of 1 and 2 against human cancer cell lines namely; MCF-7 (breast), HeLa (cervical), MIA-PA-CA 2 (pancreatic), A-498 (kidney), Hep-G2 (hepatoma) was evaluated by SRB assay. The obtained results showed that copper complex 1 was an outstanding cytotoxic agent with remarkably good GI _(50) value (<10 μg ml ~(?1) ) against the tested cancer cell lines except for MIA-PA-CA 2, while zinc complex 2 revealed moderate cytotoxicity against all the tested cancer cell lines.