Adamantyl pyran-4-one derivatives and their in vitro antiproliferative activity

Abstract

Pyran-4-one (maltol, kojic acid and chlorokojic acid 1) esters of adamantan-1-ylacetic acid were prepared through efficient synthetic routes in good yields and evaluated for their in vitro antiproliferative activity on four cancer cell lines: K562 (chronic myelogenous leukemia), HeLa (cervical cancer), Caco-2 (colorectal adenocarcinoma) and NCI-H358 (bronchioalveolar carcinoma). The results indicate that the presence and the position of the adamantyl acyl group or chlorine atom are the necessary requirement for antitumor activity of pyranone systems. Derivatives of kojic acid with either free (compounds 1 and 8) or acylated 5-OH group (compounds 2 and 9) have shown good-to-moderate activity (IC50 values ranging from 13.1 to 43.0 μM) on all cell lines. Adamantyl kojic acid derivative 5 with a free OH group on the position 2 showed activity only on the K562 cell line. It seems that removal of halogen or adamantyl unit from position 2 elicits antileukemic activity, as observed in compound 5. The positive influence of the adamantyl unit was also observed on a 3-OH acylated derivative of maltol I which was also selectively active on the same cell line. 5-O-benzylated adamantyl compounds 6 and 7 and unmodified starting pyranones were found to be inactive. Antibacterial activity of compounds was also evaluated on S. aureus ATCC 13709, M. catarrhalis ATCC 23246, E. faecalis ATCC29212 and E. coli TolC-Tn10, but no activity was observed (MIC values 128–256 µg/mL).

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Acknowledgements

We wish to thank kindly Dr Hana Čipčić Paljetak and Dr Donatella Verbanac from the School of Medicine, University of Zagreb, for investigating the antibacterial activity of compounds. We would also like to thank the Croatian Science Foundation for support of this work (Project IP-2014-09-7899).

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Correspondence to Željka Car.

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Peroković, V.P., Car, Ž., Usenik, A. et al. Adamantyl pyran-4-one derivatives and their in vitro antiproliferative activity. Mol Divers 24, 253–263 (2020). https://doi.org/10.1007/s11030-019-09948-1

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Keywords

  • Kojic acid
  • Maltol
  • Adamantyl
  • Antiproliferation
  • Cancer