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Novobiocin–ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition

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Abstract

A series of tailored novobiocin–ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC50 values in the mid-micromolar range, compounds 10a–c displayed promising antiplasmodial activity as low as 0.889 µM. Furthermore, the most promising compounds were tested for inhibitory effects against a postulated target, heat shock protein 90 (Hsp90).

Graphical abstract

A selection of tailored novobiocin derivatives bearing the organometallic ferrocene unit were synthesized and characterized by common spectroscopic techniques. The target compounds were investigated for in vitro anticancer and antimalarial activity against the MDA-MB-231 breast cancer cell line and Plasmodium falciparum 3D7 strain, respectively.

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Acknowledgements

The authors would like to acknowledge Rhodes University Sandisa Imbewu (SDK, HCH and ALE) and the National Research Foundation (MM, JNS, ALE and SDK) for financial support. Financial assistance from South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant No 98566) is also acknowledged (ALE). The South African Medical Research Council (MRC) funded the antiplasmodial bioassay component of the project with funds from National Treasury under its Economic Competitiveness and Support Package.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Rhodes University, Grahamstown, 6140, South Africa

    Mziyanda Mbaba & Setshaba D. Khanye

  2. Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Grahamstown, 6140, South Africa

    Jo-Anne de la Mare, Jason N. Sterrenberg, Deborah Kajewole, Shantal Maharaj, Adrienne L. Edkins & Heinrich C. Hoppe

  3. Biomedical Biotechnology Research Unit (BioBRU), Rhodes University, Grahamstown, 6140, South Africa

    Jo-Anne de la Mare, Jason N. Sterrenberg, Deborah Kajewole, Shantal Maharaj, Adrienne L. Edkins & Heinrich C. Hoppe

  4. Centre for Chemico- and Biomedical Research, Rhodes University, Grahamstown, 6140, South Africa

    Jo-Anne de la Mare, Adrienne L. Edkins, Michelle Isaacs, Heinrich C. Hoppe & Setshaba D. Khanye

  5. Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa

    Setshaba D. Khanye

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  1. Mziyanda Mbaba
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Correspondence to Mziyanda Mbaba or Setshaba D. Khanye.

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775_2018_1634_MOESM1_ESM.pdf

Information pertaining the synthesis and spectroscopic data of all the final compounds and intermediates investigated in this work can be found in the “Supplementary information” document (PDF 2074 kb)

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Mbaba, M., de la Mare, JA., Sterrenberg, J.N. et al. Novobiocin–ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition. J Biol Inorg Chem 24, 139–149 (2019). https://doi.org/10.1007/s00775-018-1634-9

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  • DOI: https://doi.org/10.1007/s00775-018-1634-9

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