Diorganotin(IV) complexes derived from N-terminal methylation of Triapine: synthesis, characterization and antibacterial activity evaluation

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Highlights

  • 1 and 2 were successfully synthesized and characterized.

  • The compound 1 shows a more efficient antibacterial action than standard antibacterial substances.

  • The different antibacterial activities of two compounds are due to the changes of the substituents.

  • The possible antibacterial mechanism of 1 was explored systematically.

Abstract

The reaction of diorganotin(IV) with ligands (HL1 = 3-aminopyridine-2-carbaldehyde N(4) methylthiosemicarbazone, HL2 = 3-aminopyridine-2-carbaldehyde N(4)-dimethylthiosemicarbazone) afforded two compounds [PhSn(L1)Cl2] (1) and [(Ph)2Sn(L2)Cl] (2), respectively. The compounds were characterized by elemental analysis, infrared spectrum, UV–vis spectrometry, and X-ray crystallography. The ligands and corresponding complexes were assayed for their in vitro pharmaceutical activity against different pathogenic strains of bacteria by disk diffusion method. The results demonstrate that 12 have remarkable antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). 1 exhibit higher antibacterial properties against S. aurenu (MIC = 0.00095 μg/mL) and E. coil (MIC = 0.0019 μg/mL). In the same experimental conditions, the two complexes display more potent activity relative to standard antibiotics Kanamycin and Ampicillin.

Introduction

To treat infectious diseases caused by bacteria is still an urgent and challenging public health concern. Moreover, common pathogens and new pathogenic species treated with current antibiotics develop drug resistance [1,2]. The drug resistance of bacteria leads to a reduction in the effect of some common antibiotics and may result in higher mortality and morbidity [2]. Therefore, it is inevitable to fabricate new antibacterial agents, in particular the synthesis of metal complexes with bioactive ligands.

Thiosemicarbazones containing a significant class of N, S donor are pre-eminent transition metallic chelators, having infinite interest in the coordination chemistry [[3], [4], [5]]. Thiosemicarbazones are also an important class of the carbonyl derivatives and have been proved to own versatile medicinal applications, for instance, antibacterial [6], antitumor [7], antihypertensive [8], anticonvulsant [9], antitrypanosomal [10], and antiviral agents [11]. Additionally, the function of N-terminal methylation of thiosemicarbazone complexes is crucial in the biological activities [12]. A solid example is Dp44mT (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone) and Dp4mT (di-2-pyridylketone-4-methyl-3-thiosemicarbazone). These chelators belong to the dipyridyl thiosemicarbazone (DpT) class of ligands and show different selectivity against tumor cells [13,14]. As antitumor agent, the currently most prominent representative in this family is the 3-aminopyridine-2-carbaldehyde thiosemicarbazone (Triapine), which has been investigated in clinical phase I and II studies [[15], [16], [17], [18]]. Furthermore, a variety of new derivatives have been prefabricated in recent years for the sake of improving thiosemicarbazone-based therapy.

Organotin (IV) derivatives have been widely investigated owing to their structural diversity and biological activity. Organotin (IV) compounds exhibit specificity in synthesis and structure, and their broad-spectrum applications can be attributed to ligands connected in the central tin metal atom [19]. Moreover, organotin(IV) compounds display multifunctional applications from industry, catalysis to therapeutics due to their diverse as well as fascinating structural potential [20]. Nowadays, organotin(IV) complexes formed by coordination with ligand are appealing scaffolds for new type drug research on account of their spectacular bioactivities. In recent years, many organotin(IV) complexes have been synthesized and investigated to be more remarkable than traditional metal drugs in antitumor activity [[21], [22], [23]]. Based on literatures, the biological properties are reliant on numbers and properties of organic groups, framework and ligancy of tin atom as well as the intrinsic performance of donor ligand connecting with tin metal atom [24,25]. Furthermore, some organotin(IV) compounds of Schiff bases containing a pyridine group display prominent antibacterial activities [[26], [27], [28]]. Significantly, organotin(IV) compounds may hold lower toxicity, better excretion from the body and less side effects along with no drug resistance formation compared to cisplatin analogues [29,30].

As a part of our research of Schiff based diorganotin(IV) compounds [31], herein we designed two organotin(IV) complexes, derived from HL1 and HL2 (Scheme 1). The biological activities of complexes 1 and 2, free ligands and metal precursors were evaluated by antibacterial test against two strains of E. coli and S. aureus. Antibacterial results indicated that 1 and 2 show obvious sterilizing effect. Most notably, 1 has more potent biological activity than 2 in promoting bacterial cell death and the MIC values are lower than common antibiotics Kanamycin and Ampicillin. Hence 1 as antibacterial agent has greater potential to be applied to reality.

Section snippets

Chemistry

In this paper, two complexes were synthesized by solvent evaporation method. The crystal structures of two complexes are shown in Fig. S1 and the crystal data are collected in Table S1. Bond length and bond angles are given in Table S2. These data are displayed in supplementary information. The synthesized material was confirmed by elemental analysis, infrared spectrum (IR) and UV–vis absorption spectrum, and the fluorescence emission spectra of the two products were tested.

The characteristic

Conclusion

In summary, HL1, HL2, compounds 1 and 2 are successfully synthesized and characterized. Both the ligands and its complexes exhibit good fluorescence properties. Ligands and Ph2SnCl2 exhibit desirable antibacterial activity. Meanwhile, the coordination to Sn(IV) metal atom increased antibacterial activity. 1 shows a more efficient antibacterial action than standard antibiotics Kanamycin and Ampicillin. Compound 2 has more significant bactericidal effect on E. coli. In addition to sterilization,

Materials and physical measurements

All chemicals and reagents were analytical grade and used as received without further purification. Elemental analyses of C, H and N were conducted on PerkinElmer 24000-II elemental analyzer. Infrared spectra (IR) were recorded on American Nicolet 170 Fourier infrared spectrometer. Hitachi U-4100 spectrophotometer was employed to measure the UV–vis absorption spectra. Photofluorescent spectroscopy was obtained with F-7000 Fluorescence spectrometer. X-ray crystallography was acquired with Bruker

Declaration of competing interest

The authors declare no competing interests.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (21671055) and the Program for Innovation Teams in Science and Technology in Universities of Henan Province [20IRTSTHN004].

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