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Structural characterization and antileishmanial activity of newly synthesized organo-bismuth(V) carboxylates: experimental and molecular docking studies

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Abstract

In a quest to discover new formulations for the treatment of various parasitic diseases, a series of heteroleptic triorganobismuth(V) biscarboxylates of type [BiR3(O2CR′)2], where R=C6H5 for 1–4 and p-CH3C6H4 for 5–8, were synthesized, characterized and evaluated for their biological potential against L. tropica. All the synthesized complexes were fully characterized by elemental analysis, FT-IR, multinuclear (1H and 13C) NMR spectroscopy and X-ray crystallography. The crystal structures for [BiPh3(O2CC6H4(o-Br))2] (1), [BiPh3(O2CC2H2C6H4)2] (2), [BiPh3(O2CC6H4(m-NO2))2] (3) and [BiPh3(O2CC6H4(2-OH,3-CH3))2] (4) were determined and found to have a distorted pentagonal bipyramidal molecular geometry with seven coordinated bismuth center for 1–3 and for 4 distorted octahedral geometry, respectively. All the synthesized complexes demonstrated a moderate to significant activity against leishmania parasites. A broad analytical approach was followed to testify the stability for (1–8) in solid state as well as in solution and in leishmanial culture M199, ensuring them to be stable enough to exert a significant antileishmanial effect with promising results. Cytotoxicity profile suggests that tris(tolyl) derivatives show lower toxicity against isolated lymphocytes with higher antileishmanial potential. Molecular docking studies were carried out to reveal the binding modes for (1–8) targeting the active site of trypanothione reductase (TR) (PDB ID: 4APN) and Trypanothione Synthetase-Amidase structure (PDB ID 2vob).

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Abbreviations

GOLD:

Genetic optimization for ligand docking

PBS:

Phosphate-buffered saline

CDCl3 :

Deuterated chloroform

IC50 :

The half maximal inhibition concentration

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

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Acknowledgements

The authors are thankful to Fatima Jinnah Women university and Higher Education Commission of Pakistan for the grant of funds for the project: No:21- 2465/SRGP/R&D/HEC/2019.

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Authors and Affiliations

  1. NUTECH School of Applied Sciences and Humanities, National University of Technology, Islamabad, 44000, Pakistan

    Sohaila Andleeb

  2. Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Imtiaz-ud-Din & Muhammad Khawar Rauf

  3. Department of Chemistry, Govt. Post-Graduate College Shakargarh, Shakargarh, 51800, Pakistan

    Muhammad Khawar Rauf

  4. Computational Biology Lab, National Center for Bioinformatics, Quaid-I-Aam University, Islamabad, 45320, Pakistan

    Syed Sikander Azam & Naila Zaman

  5. Department of Pharmacy, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Ihsan‐ul Haq

  6. Department of Physics, University of Sargodha, Sargodha, 40100, Pakistan

    Muhammad Nawaz Tahir

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  1. Sohaila Andleeb
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  2. Imtiaz-ud-Din
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  3. Muhammad Khawar Rauf
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775_2021_1919_MOESM1_ESM.pdf

Supplementary file1 Supporting information summary CCDC 1432780 for (1), 1411992 (2), 1832580 (3) and 1832583(4) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_ request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033. (PDF 3463 KB)

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Andleeb, S., Imtiaz-ud-Din, Rauf, M.K. et al. Structural characterization and antileishmanial activity of newly synthesized organo-bismuth(V) carboxylates: experimental and molecular docking studies. J Biol Inorg Chem 27, 175–187 (2022). https://doi.org/10.1007/s00775-021-01919-y

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