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A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study

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Abstract

New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9–11, oxadiazole, pyrazole and sulfinyl analogs 13–15, via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 μM and 91.8%, and of 79.8% at concentration of 1.0 μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity.

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Acknowledgements

We evok the spirit of Prof. W. Pfleiderer of chemistry department, University of Konstanz, Germany for providing the starting material (steroid 4).

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  1. Najim A. Al-Masoudi

    Present address: , Constance, Germany

Authors and Affiliations

  1. Department of Chemistry, College of Science, University of Al-Qadisiya, Al-Qadisiya, Iraq

    Nabeel A. Abdul-Rida & Ali M. Farhan

  2. Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq

    Najim A. Al-Masoudi

  3. Department of Chemistry, College of Education for Pure Science, University of Basrah, Basrah, Iraq

    Bahjat A. Saeed

  4. Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA

    Dannah Miller

  5. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198-5870, USA

    Ming-Fong Lin

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  1. Nabeel A. Abdul-Rida
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Abdul-Rida, N.A., Farhan, A.M., Al-Masoudi, N.A. et al. A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study. Mol Divers 25, 661–671 (2021). https://doi.org/10.1007/s11030-020-10038-w

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