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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

Abstract

New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 911, oxadiazole, pyrazole and sulfinyl analogs 1315, 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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Correspondence to Najim A. Al-Masoudi.

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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 (2020). https://doi.org/10.1007/s11030-020-10038-w

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Keywords

  • Amides
  • Anticancer activity
  • Molecular docking study
  • Oxadiazole
  • Pregnene analogs
  • Pyrazole