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Synthesis and characterization of water-soluble polyaspartamides containing platinum(II) complex and bisphosphonate as potential antimalarial drug

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Abstract

Polyaspartamides conjugates and co-conjugates containing platinum(II) complex and bisphosphonate were synthesized by stepwise reaction of polysuccinimide with selected primary amines. The first step was achieved by aminolytic ring opening of polysuccinimide and afforded conjugates containing bisphosphonate and dihydroxylato ligand for platinum chelation. In the second step conjugates were chelated to platinum(II) complex. These conjugates and co-conjugates were characterized by proton and phosphorus nuclear magnetic resonance (1H and 31P NMR), Fourier transform spectroscopy (FTIR), scanning electron microscope (SEM) and energy-dispersive X-ray analysis (EDX). The mass percentage incorporation of platinum in the co-conjugates was determined by ICP-OES and was found to be between 1.9 and 3.7 percent, while the mass percentage incorporation of bisphosphonate in the conjugates and co-conjugates was found to be between 2.5 and 3.1 percent by NMR. The preliminary pharmacological evaluation performed on co-conjugates 4, 5 and 6 revealed that co-conjugate 6 exhibited enhanced antimalarial activity than chloroquine, while co-conjugates 4 and 5 were less active.

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Acknowledgement

The financial assistance of the University of Johannesburg toward this research is hereby acknowledged.

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Authors and Affiliations

  1. Department of Applied Chemistry, University of Johannesburg, Doornfontein Campus, P.O.Box 17011, Johannesburg, Republic of South Africa

    H. E. Mukaya & X. Y. Mbianda

  2. Centre for Nanomaterial, University of Johannesburg, Doornfontein Campus, Johannesburg, Republic of South Africa

    X. Y. Mbianda

  3. Pharmacology Division, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Republic of South Africa

    R. L. van Zyl & N. J. van Vuuren

Authors
  1. H. E. Mukaya
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  2. R. L. van Zyl
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  3. N. J. van Vuuren
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  4. X. Y. Mbianda
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Correspondence to X. Y. Mbianda.

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Mukaya, H.E., van Zyl, R.L., van Vuuren, N.J. et al. Synthesis and characterization of water-soluble polyaspartamides containing platinum(II) complex and bisphosphonate as potential antimalarial drug. Polym. Bull. 74, 3161–3178 (2017). https://doi.org/10.1007/s00289-016-1886-x

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  • DOI: https://doi.org/10.1007/s00289-016-1886-x

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