Abstract

AbstractThe present research is focused on evaluation of complexation ability of Monensic acid (MonH) towards La3+ and Nd3+ ions.Changes in the SRCD spectrum of Monensinate anion were monitored upon addition of lanthanide(III) ions. The antibiotic undergoes formation of one neutral ([Ln(Mon)3(H2O)3]) and two positively charged complex species of composition [Ln(Mon)2(H2O)2]+ and [Ln(Mon) (H2O)]2+, respectively (Ln = La3+, Nd3+). Neutral complexes were isolated as fine powders and were characterized by IR, FAB-MS and ESI-MS. It is assumed that Monensin acts in bidentate coordination mode via monodentate carboxylate moiety and hydroxyl group, both located at the opposite ends of antibiotic molecule.Activity of Monensic acid and [Ln(Mon)3(H2O)3] to decrease visible bacteria growth of B. subtilis, S. Lutea and B. mycoides was evaluated by agar hole diffusion method. Results showed that complexation of lanthanide(III) ions to Monensin enhances the activity of non-coordinated ligand.Antitumor efficacy of compounds was assayed on human triple negative breast cancer and transplantable sarcoma in rat. The cytotoxicity was accessed by MTT test, NR uptake, CV assay and double AO/PI staining. Experimental data revealed that Monensic acid and [Ln(Mon)3(H2O)3] possess concentration- and time-dependent activity, and express promising cytotoxic properties against human and rat permanent cancer cell lines.

Highlights

  • Polyether ionophores (PI) as Monensin, Salinomycin, Maduramycin, Narasin, Lasalocid, etc., represent a large group of natural biologically active compounds, produced by Streptomyces spp

  • Dimethyl sulfoxide (DMSO), crystal violet, propidium iodide (PI), acridine orange (AO) and trypsin were purchased from AppliChem (Darmstadt, Germany)

  • Permanent cell lines established from human triple negative breast cancer (MDA-MB-231) and transplantable rat sarcoma induced by the Rous sarcoma virus strain Schmidt-Rupin (LSR-SF-SR) were used as model systems in cytotoxicity assays

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Summary

Introduction

Polyether ionophores (PI) as Monensin, Salinomycin, Maduramycin, Narasin, Lasalocid, etc., represent a large group of natural biologically active compounds, produced by Streptomyces spp. They show an outstanding potency for the control of coccidiosis caused by protozoan Eimeria parasites - a disease, which has been for a long time the major cause of poor performance and lost productivity in poultry and other farm animals. The present paper reports new data on the coordination of Monensic acid with ions of La3+ and Nd3+, spectral characterization of corresponding metal(III) complexes and their antimicrobial / antitumor properties

Materials
Methods
Antibacterial activity
Cytotoxicity assays
Statistical analysis
Spectral properties of Monensinate complexes
Biological activity of Monensic acid and complexes 1-2
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