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Synthesis and structural elucidation of two new series of aurone derivatives as potent inhibitors against the proliferation of human cancer cells

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Abstract

Two new series of aurone compounds were synthesized via an oxidative cyclization reaction of 2′-hydroxy-chalcones. Series (A) consists of 1a–3a aurones with different substitutions on a B-ring at position 4′, and series (B) is made up of 1b–3b aurones that have different substitutions at position 2′ of a B-ring. Structures of the synthesized compounds were characterized and confirmed by FTIR (1D and 2D NMR) and EI mass spectral studies. The molecular structure of 2b was further confirmed by the X-ray crystallographic technique, with the compound found to be in Z-isomeric form. The compounds of both series were tested for their antiproliferative activity against human colorectal tumor (HCT 116), human chronic myelogenous leukemia (K562) and hormone-dependent breast cancer (MCF-7) cell lines according to an MTT assay. Series (B) exhibited a higher cytotoxic effect on the cancer cell lines compared to series (A). Selectively, the most promising results have been shown by the two most active compounds, 1b (Z-5,7, 2′-trichloro-aurone), which resulted in IC50 values of 36, 23 and 23 μM against HCT 116, MCF-7 and K562 cancer cells, respectively. Compound 3a (Z-5, 7-dichloro-4′-methyl-aurone) exhibited the highest activity against the K562 cell line (IC50 = 20 μM), which can be compared to that of the standard drug, betulinic acid, with an IC50 value of 15 μM. The results of the present study suggested that aurone derivatives emerged as a potential candidate for the development of future chemotherapeutic agents.

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Acknowledgments

We thank Universiti Sains Malaysia (USM) for functional support through a Research University (RU) Grant (1001/PKIMIA/811221). The authors would also like to acknowledge the RU Grant of USM (RUT 1001/PKIMIA/855006) for financial support for the project. Aboubaker A. Elhadi thanks the Libyan government for the Ph.D. scholarship.

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Authors and Affiliations

  1. School of Chemical Sciences, Universiti Sains Malaysia, 11800, Minden, Pulau Pinang, Malaysia

    Aboubaker A. Elhadi, Hasnah Osman & Muhammad Adnan Iqbal

  2. EMAN Research and Testing Laboratories, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Pulau Pinang, Malaysia

    Sharmila K. Rajeswari, Mohamed B. Khadeer Ahamed & Amin M.S. Abdul Majid

  3. X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800, Minden, Pulau Pinang, Malaysia

    Mohd Mustaqim Rosli & Ibrahim Abdul Razak

  4. Advanced Medical and Dental Institute (IPPT), University Sains Malaysia, 11800, Minden, Pulau Pinang, Malaysia

    Aman Shah Abdul Majid

Authors
  1. Aboubaker A. Elhadi
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  2. Hasnah Osman
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  3. Muhammad Adnan Iqbal
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  4. Sharmila K. Rajeswari
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  5. Mohamed B. Khadeer Ahamed
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  6. Amin M.S. Abdul Majid
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  7. Mohd Mustaqim Rosli
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  8. Ibrahim Abdul Razak
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  9. Aman Shah Abdul Majid
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Correspondence to Hasnah Osman.

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Elhadi, A.A., Osman, H., Iqbal, M.A. et al. Synthesis and structural elucidation of two new series of aurone derivatives as potent inhibitors against the proliferation of human cancer cells. Med Chem Res 24, 3504–3515 (2015). https://doi.org/10.1007/s00044-015-1400-2

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  • DOI: https://doi.org/10.1007/s00044-015-1400-2

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