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Development of new hetero-steroid hybrids with antiproliferative activity against MCF-7 breast cancer cells

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Abstract

In continuation of our efforts to develop new antiproliferative agents that could be effective and selective in treatment of cancer, we designed and synthesized new hybrid structures containing an arylsulfonamide scaffold linked to a steroidal skeleton through a 1,2,3-triazole ring. Both in vitro cytotoxicity on breast MCF-7 cancer cells and human placental aromatase enzyme (pAROM) inhibition assays were performed on new hybrids. All new hybrids showed marked cytotoxic activity against breast MCF-7 cancer cells (IC50 = 3.56–43.76 μM) in comparison to staurosporine (IC50 = 4.06 μM). Tumor selectivity index was higher for some of the new hybrids on normal fibroblast (F-180) cells (TS = 1.5–25) in comparison to staurosporine (TS = 2.5). The p-nitro derivative exhibited the best inhibitory activity on the pAROM with an IC50 of 64.6 ng/cm3, compared to hybrids unsubstituted derivative, p-bromo derivative, and letrozole (IC50 = 375.14, 269.86, and 132.86 ng/cm3, respectively). Furthermore, the p-nitro hybrid arrested the cell cycle selectively at the G2/M phase, in addition to inducing both early and late apoptotic processes of breast MCF-7 cancer cells. Molecular docking studies were performed within pAROM to explore the binding modes of the new hybrids. Collectively, the antiproliferative profile of new hybrids indicates how good they are as promising leads for developing tumor-specific cytotoxins, and deserve further studies to optimize their structure and in vivo activity.

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Acknowledgements

Special thanks to Prof. Gamal Abu-Rahmah, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Minia University for his advises through the research work, also to Dr. Abu-Baker Mostafa, Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University for his guidance through chemistry part, and finally, for Dr. A. Y. Desoky, Department of Chemistry, Faculty of Science, the University of Waterloo for running mass spectral analysis for our group.

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Authors and Affiliations

  1. Medicinal Chemistry Department, Faculty of Pharmacy, Deraya University, Minia, 61111, Egypt

    Muhamad Mustafa

  2. Faculty of Pharmacy, Student Research Center, Assiut University, Assiut, 71526, Egypt

    Ahmed El-Kardocy

  3. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt

    Yaser A Mostafa

Authors
  1. Muhamad Mustafa
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  2. Ahmed El-Kardocy
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  3. Yaser A Mostafa
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Correspondence to Yaser A Mostafa.

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Mustafa, M., El-Kardocy, A. & Mostafa, Y.A. Development of new hetero-steroid hybrids with antiproliferative activity against MCF-7 breast cancer cells. Monatsh Chem 152, 137–149 (2021). https://doi.org/10.1007/s00706-020-02716-0

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  • DOI: https://doi.org/10.1007/s00706-020-02716-0

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