Issue 1, 2020

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

Abstract

New RNA targeted ionic [Cu(DACH)2(H2O)2](mef)2, 1 and [Zn(DACH)2(H2O)2](mef)2, 2 drug conjugates were synthesized and characterized by spectroscopic techniques FT-IR, UV-vis, EPR in case of 1 and 1H and 13C 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, Kb = 2.52(±0.04) × 105 M−1, 7.85(±0.02) × 104 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 GI50 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.

Graphical abstract: 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

Supplementary files

Article information

Article type
Paper
Submitted
16 Sept. 2019
Accepted
12 Dec. 2019
First published
24 Dec. 2019
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 166-178

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

H. Y. Khan, S. Tabassum and F. Arjmand, RSC Adv., 2020, 10, 166 DOI: 10.1039/C9RA07464C

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