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Structural analysis and antitumor potential of novel 5,6-disubstituted-17a-homo-17-oxa-androstane derivatives

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Abstract

Starting from 3β-acetoxy-17a-homo-17-oxa-androst-5-en-16-one (1) and in the reaction with N-bromoacetamide (NBA) and perchloric acid, the 5α-bromo-6β-hydroxy (2), 5β,6β-epoxy (3) and 5α,6β-dibromo (4) derivatives were obtained. The structure of compounds 2–4, particularly stereochemistry at C5 and C6, is established by detailed NMR and X-ray analysis. The in vitro antiproliferative activity of newly synthesized compounds 2–4 against six human tumor cell lines was evaluated. All three compounds showed a significant toxicity toward hormone-independent breast adenocarcinoma MDA-MB-231 and cervical carcinoma cells HeLa, while dibromo derivative 4 was active toward five human cancer cell lines. These new 5,6-disubstituted-D-homolactone steroidal compounds have also displayed selectivity toward cancerous cell lines against inactivity found for noncancerous control cell line. This selectivity was not found for control compound, well-known chemotherapy drug cisplatin.

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Acknowledgments

We thank the Ministry of Education, Science and Technological Development of the Republic of Serbia for financial support (Grant No. 172021).

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Authors and Affiliations

  1. Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad, 21000, Serbia

    Ivana Kuzminac, Dušan Škorić & Marija Sakač

  2. Department of Physics, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 4, Novi Sad, 21000, Serbia

    Olivera R. Klisurić

  3. Oncology Institute of Vojvodina, Put Dr Goldmana 4, Sremska Kamenica, 21204, Serbia

    Dimitar Jakimov

Authors
  1. Ivana Kuzminac
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  2. Olivera R. Klisurić
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  3. Dušan Škorić
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  4. Dimitar Jakimov
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  5. Marija Sakač
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Corresponding author

Correspondence to Ivana Kuzminac.

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Kuzminac, I., Klisurić, O.R., Škorić, D. et al. Structural analysis and antitumor potential of novel 5,6-disubstituted-17a-homo-17-oxa-androstane derivatives. Struct Chem 28, 567–576 (2017). https://doi.org/10.1007/s11224-016-0815-9

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  • DOI: https://doi.org/10.1007/s11224-016-0815-9

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