Details

Autor(en) / Beteiligte

• Yasir Khan, Huzaifa
• Tabassum, Sartaj
• Arjmand, Farukh

Titel

Preparation and characterization of ionic metal-based anticancer formulations of the type [bis-DACH tolfenamate metal {Co(II), Cu(II) and Zn(II)}] complexes: Binding studies with ct-DNA/tRNA, cleavage and cytotoxic activity against chemoresistant cancer cells

Ist Teil von

• Inorganica Chimica Acta, 2023-12, Vol.558, p.121725, Article 121725

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Three Co(II), Cu(II) and Zn(II) ionic metal-based complexes were synthesized. Copper complex had a higher affinity for tRNA, resulting in efficient suppression of resistant breast cancer strains at extremely low micromolar concentrations. [Display omitted] •Ionic metallo-NSAID’s having the formulae [M(DACH)2(H2O)2](tolf)2 were synthesized and characterized.•The structure of complexes was optimized by spartan computational programme package.•Complexes exhibited distinct preferential selectivity for tRNA in comparison to ct–DNA.•The copper complex 2 showed good cytotoxic response against the tested cancer cell lines. A series of ionic metallo-NSAID’s having the formulae [Co(DACH)2(H2O)2](tolf)21, [Cu(DACH)2(H2O)2](tolf)22 and [Zn(DACH)2(H2O)2](tolf)23 where DACH and tolf− are 1,2-diaminocyclohexane and tolfenamate anion, respectively were synthesized. Complexes 1–3 were characterized by FT–IR, EPR, 1H/13C NMR, UV–vis and ESI–MS spectrometry methods. The bonding features as well as the electronic structure of all the complexes were optimized using DFT studies. Binding affinity of parent NSAID and 1–3 complexes with ct–DNA/tRNA were studied by using various complementary biophysical methods. The corroborative results of these experimental studies revealed that they were capable to interact with the therapeutic targets, ct–DNA/tRNA by the electrostatic interactions, showing higher preference for tRNA as compared to ct–DNA as quantified by their binding strength (Kb and Ksv values). It was also observed that the complexes exhibited much higher binding affinity than the parent free NSAID. A concentration-dependent cleavage of the complexes was observed with tRNA which promoted the hydrolysis of RNA. The cytotoxicity of 1–3 was evaluated against chemo-resistant phenotypes of cancers, viz., breast cancer cell line (MCF- 7), cervical cancer cell line (SiHa), triple-negative breast cancer cell (MDA-MB-231), oral squamous cancer cell (AW13516) and lung cancer cell line (Hop-62) by SRB assay. The cytotoxicity activity results displayed that among all the ionic tolfenamate metal complexes, complex 2 showed a much superior cytotoxic profile against treated cancer cell lines (SiHa, MDA-MB-231, AW13516, MCF-7 and Hop-62) with a good GI50 value of (4.7 ± 0.03) µg/ml, (10.5 ± 0.36) µg/ml, (19.2 ± 0.02) µg/ml, (4.1 ± 0.05) µg/ml, and (18.2 ± 0.04) µg/ml, respectively, while the complexes 1 and 3 showed moderate activity. Cell morphology studies were carried out in AW13516, MDA–MB–231, MCF–7 and Hop–62 cells with the incubation of complexes for a period of 48 h which implicated that the cells exposed to complex 2 presented round features and were nonadherent in culture. These morphological changes indicated that complex 2 was capable of inducing cell death, probably by apoptosis suggesting copper complex 2 was promising potent anticancer agent.