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Effective inhibition of insulin amyloid fibril aggregation by nickel(II) complexes containing heterocyclic thiosemicarbazones

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Abstract

The sensitivity of protein molecular structures makes them susceptible to aggregation in conditions unfavorable for the maintenance of their native folds. The aggregation of proteins leads to many disorders, but the inhibition of amyloid fibril formation using metal-containing small molecules is gaining popularity. Herein we report the effect of nickel(II) complexes (N1, N2, N3, and N4) bearing thiosemicarbazones on the inhibition of amyloid fibril formation by insulin. The interactions of the complexes with amyloid fibrils were investigated using various biophysical techniques, including light scattering, intrinsic fluorescence assay, thioflavin T (ThT) assay, and Fourier transform-infrared spectroscopy. The results revealed that the phenyl-substituted N3 was an efficient inhibitor of amyloid fibril formation and maintained the insulin in its native structure despite conditions promoting fibrillation.

Graphic abstract

Nickel(II) complexes containing indole based thiosemicarbazones were efficient in inhibiting the amyloid fibril formation and maintaining the insulin in its native structure in unfavorable conditions.

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Acknowledgements

K.G. and S.S thanks Dr. MGR Educational and Research Institute for giving enough infrastructure to complete this work. J.H. thanks the Fondo Nacional de Ciencia y Tecnologia (FONDECYT) (3200391 and 11170840).

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Author notes

  1. Kannayiram Gomathi and Jebiti Haribabu have contributed equally to this work.

Authors and Affiliations

  1. Department of Mechanical Engineering, Dr. MGR Educational and Research Institute, Maduravoyal, Chennai, 600095, India

    Kannayiram Gomathi, Sivaraj Saranya & Subramanian Sendilvelan

  2. Department of Chemistry, National Institute of Technology, Tiruchirappalli, 620015, India

    Jebiti Haribabu, Kumaramangalam Jeyalakshmi & Ramasamy Karvembu

  3. Facultad de Medicina, Universidad de Atacama, Copayapu 485, 1531772, Copiapo, Chile

    Jebiti Haribabu & Cesar Echeverria

  4. Multi Organ Transplant Program, University Health Network, Toronto, Canada

    Sivaraj Saranya

  5. Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, 600025, India

    Dasararaju Gayathri

  6. Department of Chemistry, M. Kumarasamy College of Engineering, Karur, 639113, India

    Kumaramangalam Jeyalakshmi

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  1. Kannayiram Gomathi
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Gomathi, K., Haribabu, J., Saranya, S. et al. Effective inhibition of insulin amyloid fibril aggregation by nickel(II) complexes containing heterocyclic thiosemicarbazones. Eur Biophys J 50, 1069–1081 (2021). https://doi.org/10.1007/s00249-021-01566-w

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  • DOI: https://doi.org/10.1007/s00249-021-01566-w

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