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Synthesis, antiproliferative activity, and molecular docking studies of curcumin analogues bearing pyrazole ring

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Abstract

Several curcumin analogues bearing pyrazole were synthesized and characterized by IR, NMR, and mass spectral data. There were four tested compounds among 11 synthesized compounds, which were evaluated for antiproliferative activity and showed significant activity in both one-dose and five-dose assays. The antiproliferative effects were tested on a panel of 60 cell lines, according to the National Cancer Institute screening protocol. The most active compounds among the series were 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-carboxamide (3k) which showed mean percent growth inhibition of 116.09 in one-dose assay at 10 µM, and GI50 values were ranging between 0.0912 and 2.36 µM in five-dose assay. The best results were recorded on the leukaemia cell lines with value ranging from 0.0912 to 0.365 µM. All the tested compounds showed broad-spectrum antiproliferative activity over different cancer cell lines. When compared with the standard drug paclitaxel, the compound 3k showed superior activity on nearly 42 cell lines. The molecular docking study was performed to explore the binding interaction of these curcumin analogues with the active site of EGFR tyrosine kinase (EGFR-TK). The hydroxyl group of both phenyl rings was important for the rein-geminated hydrogen bonding by either side chain or backbone with the active site of EGFR-TK.

Graphical Abstract

Four curcumin analogues were evaluated for their antiproliferative activity and showed promising results. The molecular docking studies showed that all the compounds (3a–k) were well accommodated in the EGFR tyrosine kinase.

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Acknowledgments

Antiproliferative data were provided by National Cancer Institute (NCI US), Bethesda, MD, USA. We are grateful for all help provided by Prof. Doug Smallwood and Mr. Mohammed Nayel. The people holding the management of Maharishi Arvind College of Pharmacy, Jaipur, Rajasthan, India, are acknowledged for providing research facilities. We are also grateful to Dr. Reddy Institute of Life Science, Hyderabad, Andhra Pradesh, India, for providing spectral data of synthesized compounds.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari, Jaipur, Rajasthan, 302 039, India

    Mohamed Jawed Ahsan & Kavita Choudhary

  2. Department of Pharmaceutical Chemistry, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835 215, India

    Surender Singh Jadav & Sabina Yasmin

  3. Pharmacoinformatics Department, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, 844 102, India

    Md. Yousuf Ansari

  4. Department of Chemistry, Acharya Nagarjuna University, Nagarjuna Nagar, 522 510, India

    Reddymasu Sreenivasulu

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  1. Mohamed Jawed Ahsan
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  2. Kavita Choudhary
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  3. Surender Singh Jadav
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  4. Sabina Yasmin
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  5. Md. Yousuf Ansari
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  6. Reddymasu Sreenivasulu
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Correspondence to Mohamed Jawed Ahsan or Kavita Choudhary.

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Ahsan, M.J., Choudhary, K., Jadav, S.S. et al. Synthesis, antiproliferative activity, and molecular docking studies of curcumin analogues bearing pyrazole ring. Med Chem Res 24, 4166–4180 (2015). https://doi.org/10.1007/s00044-015-1457-y

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