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Synthesis, Characterization, Optical Properties, Molecular Modeling and Urease Inhibition Analysis of Organic Ligands and Their Metal Complexes

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Abstract

Recently, screening of efficient urease inhibitors by employing organic small molecules metalloderivatives interests the scientific community due to their efficacy for treatment of urease triggered health complications. This study comprises the synthesis, urease inhibition activity, optical analysis and molecular modeling of hydrazinecarbothioamide and hydrazinecarboxamide metalloderivatives. Characterization of synthesized materials was done by UV-visible, fluorescence, NMR and FTIR spectroscopic analysis. Metalloderivatization of ligands induce increment in urease inhibition potential and effect was prominent for copper complexes with 10-fold enhancement, cobalt complex with 3.5 fold’s enhancement and palladium with 2-fold increment in the inhibition efficacy toward urease when it was compared with reference urease inhibitor. Zinc and iron complexes cause declined urease inhibition activity of the bare ligand. The overall activity of hydrazinecarbothioamide slightly exceeds than that of hydrazinecarboxamide, possibly due to larger complexation ability of sulfur-based ligand in comparison to oxygenated derivatives i.e., hydrazinecarboxamide. The enzyme inhibition kinetics for the most active complexes represent the mixed type urease inhibition for 3a and competitive urease inhibition for 5a, as determined by Lineweaver–Burk plots. The docked scoring values for both the ligands were calculated to be 61.34, 64.72, 56.68, 62.94, 64.98 and 58.98. Three active hydrogen bonds were observed in docking complex upon computational analysis of most potent metallodrug 3a inside active region of targeted protein.

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Acknowledgements

Authors acknowledge University of Sargodha for the availability of necessary setup and instrumentation for carrying out this research work.

Funding

This Research work was supported by the University of Sargodha and Thal University Bhakkar.

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Authors and Affiliations

  1. Department of Chemistry, University of Sargodha, Sargodha, Pakistan

    Muhammad Saleem

  2. Department of Chemistry, Thal University Bhakkar, 30000, Bhakkar, Pakistan

    Muhammad Saleem

  3. Department of Chemistry, GC University Faisalabad, Sub campus layyah-31200, Faisalabad, Pakistan

    Muhammad Hanif

  4. Department of Physiology and Biochemistry, Cholistan University of Veterinary and Animal Sciences, 6300, Bahawalpur, Pakistan

    Muhammad Rafiq

  5. Institute of Molecular biology and Biotechnology/(IMBB), The University of Lahore, 1-KM, Defence Road, Bhubtian Chowk, Lahore, Pakistan

    Mubashir Hassan

  6. Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, 6300, Bahawalpur, Pakistan

    Tehreem Tahir

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Material collection, data collection and analysis were performed by Muhammad Saleem and Muhammad Hanif. Draft proof reading and editing was done by Muhammad Rafiq and Tehreem Tahir. Mubashir Hassan has performed molecular docking analysis.

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Correspondence to Muhammad Saleem.

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Saleem, M., Hanif, M., Rafiq, M. et al. Synthesis, Characterization, Optical Properties, Molecular Modeling and Urease Inhibition Analysis of Organic Ligands and Their Metal Complexes. J Fluoresc 33, 113–124 (2023). https://doi.org/10.1007/s10895-022-03032-y

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