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Synthesis, structural, pharmacological and molecular docking simulations studies of some transition metal complexes

https://doi.org/10.1016/j.inoche.2020.108271Get rights and content

Highlights

  • Synthesis and Characterisation of Cu(II),Ni(II),Co(II),Mn(II) and Zn(II) complexes were carried out.

  • Pharmacological activities of chelates possess enhanced activity than free ligand.

  • Potential antimicrobial scenery of synthesized complexes.

  • Doping of the synthesized compounds with protein using HEX-8.0 software.

Abstract

Neutral [CuL2], [NiL2], [CoL2], [MnL2] and [ZnL2] complexes were synthesized using Schiff base derived from Benzalidene-4-imino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one and tyrosine. All the compounds were characterized by elemental analysis, magnetic susceptibility, ESI-Mass spectra, Powder XRD, SEM, FTIR, UV–Vis., 1H & 13C NMR, EPR and Cyclic voltammogram techniques. The general formula of the complexes [ML2] was confirmed by analytical data and ESI-mass spectra. The polycrystalline nature of the complexes was proved by powder XRD and surface morphology studies ensure that the complexes exist in nano size grain. The octahedral geometry of synthesized complexes was examined by magnetic susceptibility measurements and electronic absorption spectra. ESR parameters of copper complex clearly indicate that the complex is axially elongated octahedral geometry. Pharmacological activities like analgesic, antipyretic, anti-inflammatory and CNS activities of Schiff base and its metal complexes were studied using albino mice which show that chelates have higher activities than free ligand. The good antioxidant activity of chelates was observed through DPPH free radical scavenging assay method. The antimicrobial activities of Schiff base and its complexes reveal that the complexes have superior antimicrobial activity than Schiff base. The DNA binding interaction study of [CuL2] by UV–Vis. spectroscopy shows the strong binding of [CuL2] complex on DNA with high binding constant value (Kb = 7.4 × 105) and the respective binding occurs through intercalation mode. The prediction of activity spectra of substance (PASS) expounds the drug-like nature of the compound. The in silico ADMET studies expose that Schiff base acquires enhanced biological potential. This was further confirmed by molecular docking studies of complex with DNA and (PDB ID: 6COX) protein.

Introduction

Transition metal Schiff base complexes of 4-aminoantipyrine derivative have been extensively studied due to their wide applications in various fields like biological, pharmacological, clinical, analytical and industrial area [1]. The chelating abilities, analytical and biological applications of these compounds are remarkably attract the young researchers [2]. 4-aminoantipyrine was used as a non-steroidal anti-inflammatory drug, non-narcotic analgesic, anti-rheumatic drug and peripheral nervous system drug. The biological abilities of 4-aminoantipyrine were improved by condensing it with aldehyde/amines and further chelating with biologically potent metal ions. Amino acids have both amino and acid functional groups which play a most important role in structure of body, construction of muscle tissue, physiology like energy storage/recovery, brain function, strength and fat loss. Among the various amino acids, tyrosine plays an important role for making the body's protein and thyroxin. It acts as reducer of stress, precursor for hormones and fundamental human pigment. Because of these biological essentialities, we chose both 4-aminoantipyrine and tyrosine as a basic moiety in our work [3], [4]. Earlier works reported that synthesis, characterization and antimicrobial studies on transition metal complexes of 4-aminoantipyrine derivatives. But, we are very much interested in the pharmacological studies of Schiff base transition metal complexes. Literature investigation reveals that no work has been done on the condensation of benzalidene-4-iminoantipyrine with tyrosine [5]. Hence, we report herein the synthesize, structural depiction and biological studies of Schiff base Cu(II), Co(II), Ni(II), Mn(II) and Zn(II) complexes obtained by condensation of benzalidene-4-iminoantipyrine and tyrosine. Furthermore, the investigated compounds were used to test various pharmacological activities like antioxidant assay, analgesic, antipyretic, anti-inflammatory, CNS depressant activity, antioxidant assay and antimicrobial studies. Such pharmacological activities of compounds were theoretically confirmed through molecular docking simulations studies.

Section snippets

Materials and methods

Chemicals used in this work were purchased from E-Merck analar grade samples [Solvents, 4-aminoantipyrine, Benzaldehyde, tyrosine and metal chlorides (CuCl2/NiCl2/CoCl2/MnCl2/ZnCl2)]. Solvents used for various studies were purified as per standard procedure. Elemental analysis was carried out by using thermal finger-flash CA, 112 series. Electronic spectra of the samples were recorded by using Shimadzu model (UV-1700) spectrophotometer and IR spectra were recorded on FT-IR Shimadzu model

Results and discussion

The physical characterization and elemental analysis of synthesized compounds are made known in Table 1.

The analytical data indicate that entire complexes are mononuclear with the general formula [ML2], where M = Cu(II), Ni(II), Co(II), Mn(II) and Zn(II) and L = C27H25N4O3. The non-electrolytic environment of the metal complexes was confirmed through their lower molar conductance data [12]. The magnetic susceptibility data reveal that [CuL2], [NiL2], [CoL2] and [MnL2] complexes are paramagnetic

Conclusions

Based on the above studies, it is concluded that metal chelates [CuL2], [NiL2], [CoL2], [MnL2] and [ZnL2] were synthesized by using the Schiff base derived from Benzalidene-4-imino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one and tyrosine. The analytical and spectral data of the complexes correspond well to the general formula [ML2] with octahedral geometry. The powder XRD data and SEM images suggest that the complexes are polycrystalline with nano grain sized structure. Non-electrolytic nature of

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors express sincere thanks to the Principal and Head of the department of chemistry, Raja Doraisingam Government Arts and Science College, Sivagangai for providing research facilities. One of the authors (A.K.) is grateful to Principal, Head and faculty members, Department of chemistry for their support.

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