Antibacterial and molecular study of thiourea derivative ligand and its Dimethyltin(IV) complex with the superior of its Copper(II) complex as a hepatocellular antitumor drug

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Abstract

1-benzoyl(1,2,4-triazol-3-yl)thiourea [BTThU] ligand and its [dimethyltin(IV), Pd(II) and Cu(II)] complexes are synthesized. The complexes are formed in molar ratio Cu(BTThU)2, DMT(BTThU)2 and Pd(BTThU)2. The characterization has been done by using different physicochemical methods as elemental analyses, IR, 1H NMR DMSO‑d6 and molar conductance measurements. The stability constants of the formed species that produced from the interaction of [BTThU] with dimethyltin(IV) [DMT], dibutyltin(IV) [DBT] and diphenyltin(IV) [DPT] were determined potentiometrically using the non-linear least-square program MINIQUAD-75 in 50% ethanol–water mixture and 0.1 M ionic strength at 25 °C. Concentration distribution diagrams for these system were evaluated. The theoretical conformational structure analyses were performed using density functional theory for thiol and thione tautomeric forms of [BTThU] ligand and its complex at B3LYP functional with 6-311G basis set for ligand and LANL2DZ basis set for complex. The theoretical vibrational frequency values of the optimized structures were calculated. The charge distribution within the ligand and its dimethyltin(IV) complex was calculated using Mulliken population analysis of [MPA] and natural population analysis [NPA]. The biological activity of BTThU ligand and its dimethyltin(IV) complex were tested in vitro against some selected species of fungi and bacteria. The hepatocellular antitumor effect of all compounds was investigated.

Introduction

Cancer is one of the main causes of mortality and morbidity in world. Metal-based antitumor drugs play a relevant role in antiballistic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. Among non-Pt compounds, it was of considerable interest to develop novel antitumor Pd(II) complexes as the coordination chemistry of Pd(II) and Pt(II) is usually similar. Also, organotins are gaining more attention as anti-cancer agents due to their potent cytotoxicity properties [1] and copper complexes are potentially attractive as anticancer agents [2]. Copper complexes have attracted attention based on modes of action different from that of cisplatin (covalent binding to DNA). Therefore, copper complexes may provide, at least in principle, a broader spectrum of antitumor activity [2]. Heterocyclic compounds play one of the most important roles in modern medicinal compounds. One series of heterocyclic compounds of particular interest are Schiff bases of 1,2,4-triazoles that shows an important spectrum of biological uses [[3], [4], [5]] because of its an electron rich model so, it readily binds with a many enzymes and receptors in biological systems. Benzoyl derivatives of thiourea have gained a great deal of importance in the present day [6]. Thiourea linkages have contributed greatly to the observed enhancement in various activities including anticancer [7], antiviral [8], antibacterial [[9], [10], [11], [12]], antifungal [13] and antimalarial [14,15]. Therefore the combination between these two biologically active scaffolds is a chance to give a new compound of expected an acceptable biological activity, viz. [BTThU] 1-benzoyl(1,2,4-triazol-3-yl) thiourea. Extensive studies were done on organotin(IV) coordination geometries and their structural diversity (monomeric, dimeric, hexameric, and oligomeric) [16]. They showed success in the area of inorganic and metal organic chemistry through pharmacological [17,18] (antifungal, antibacterial and antitumor drugs) applications. So referring to the huge applications of the organotin(IV) complexes [19,20] specially the antibacterial and antifungal, It was of interest to investigate some of new tin complexes with 1-benzoyl(1,2,4-triazol-3-yl) thiourea. This investigation provides a new opportunity for the development of novel antimicrobials to overcome the ever increasing of drug resistance problem.

Section snippets

Experimental

Dimethyltin(IV) dichloride [DMT], diphenyltin(IV) dichloride [DPT] and dibutyltin(IV) dichloride [DBT] were obtained from Merck Chem. CuCl2·2H2O and Na2PdCl4 obtained from Sigma Chem. Co. Carbonate-free NaOH (titrant) was used for the standardized against potassium hydrogen phthalate solution.

Solid complexes characterization

The chemical composition of the dimethyltin(IV) complex was characterized by elemental analysis. The data is supporting the formation of 1:2 complex (dimethyltin(IV): ligand). The molar conductance of the complex solution is very low value indicating that the complex is having nonelectrolyte nature. This indicated that the complex is self-neutralized by the attached ligands with the absence of any ionic chloride ions in the outer sphere of the complex, therefore the ligand coordinated as

Conclusions

The present work investigates the synthesis of a thiourea derivative having a triazole and benzoyl groups [BTThU] and its dimethyltin(IV) complex. The calculation of the charge distribution within the ligand and its dimethyltin(IV) complex Mullikan population analysis [MPA] and natural population analysis [NPA] suggests that upon coordination of 1-benzoyl(1,2,4-triazol-3-yl)thiourea [BTThU] molecule to dimethyltin(IV) moiety, the electron density is concentrated around coordinating oxygen and

References (46)

  • J.J. Criado et al.

    J. Inorg. Biochem.

    (1998)
  • M. Eweis et al.

    Int. J. Biol. Macromol.

    (2006)
  • T.S. Basu Baul et al.

    J. Inorg. Biochem.

    (2012)
  • A. Kumar et al.

    Main Group Chem.

    (2016)
  • P. Gans et al.

    Inorg. Chim. Acta.

    (1976)
  • G. Berger

    Comput. Theor. Chem.

    (2013)
  • M. Naseh et al.

    Comput. Theor. Chem.

    (2013)
  • M.J. Burkitt

    Methods Enzymol.

    (1994)
  • N. Awang et al.

    PJBS

    (2011)
  • C. Marzano et al.

    Anticancer Agents Med. Chem.

    (2009)
  • D.C. Schroeder

    Chem. Rev.

    (1955)
  • R.P. Rao

    Indian J. Appl. Chem.

    (1960)
  • I. Fakhar et al.

    Chem. Cent. J.

    (2017)
  • M.G. Mostafa et al.

    Chem. Cent. J.

    (2016)
  • C.W. Sun et al.

    Chin. J. Struct. Chem.

    (2007)
  • A. Saeed et al.

    Turk. J. Chem.

    (2010)
  • L.K. Ahmadi et al.

    J. Nanostruct. Chem.

    (2017)
  • S. Kumar et al.

    New J. Chem.

    (2017)
  • H. Pasdar et al.

    Molecules

    (2017)
  • T.J. Egan et al.

    J. Med. Chem.

    (2004)
  • K.R. Koch et al.

    J. Chem. Soc. Dalton Trans.

    (1998)
  • Y.F. Win et al.

    J. Chem. Crystallogr.

    (2008)
  • R. Joshi et al.

    J. Coord. Chem.

    (2008)

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