2. Academic Validation
  3. Synthesis, biological evaluation and quantitative structure-active relationships of 1,3-thiazolidin-4-one derivatives. A promising chemical scaffold endowed with high antifungal potency and low cytotoxicity

Synthesis, biological evaluation and quantitative structure-active relationships of 1,3-thiazolidin-4-one derivatives. A promising chemical scaffold endowed with high antifungal potency and low cytotoxicity

  • Eur J Med Chem. 2017 Nov 10:140:274-292. doi: 10.1016/j.ejmech.2017.09.026.
Simone Carradori 1,  Bruna Bizzarri 2,  Melissa D'Ascenzio 2,  Celeste De Monte 2,  Rossella Grande 3,  Daniela Rivanera 4,  Alessanda Zicari 5,  Emanuela Mari 5,  Manuela Sabatino 6,  Alexandros Patsilinakos 7,  Rino Ragno 7,  Daniela Secci 8
Affiliations

Affiliations

  • 1 Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy. Electronic address: simone.carradori@unich.it.
  • 2 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
  • 3 Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; Center for Aging Science and Translational Medicine (CeSI-MeT), Via dei Vestini 31, 66100 Chieti, Italy.
  • 4 Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
  • 5 Dipartimento di Medicina Sperimentale, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
  • 6 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Rome Center for Molecular Design, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
  • 7 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Rome Center for Molecular Design, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Alchemical Dynamics s.r.l., 00125 Rome, Italy.
  • 8 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: daniela.secci@uniroma1.it.
PMID: 28963991 DOI: 10.1016/j.ejmech.2017.09.026
Abstract

With reference to recent studies reporting on the various biological properties of the thiazolidinone scaffold, we synthesized more than a hundred compounds characterized by a 1,3-thiazolidin-4-one nucleus derivatised at the C2 with a hydrazine bridge linked to (cyclo)aliphatic or hetero(aryl) moieties, and their N-benzylated derivatives. These molecules were assayed as potential anti-Candida agents and they were shown to possess comparable, and in some cases higher biological activity than well-established topical and systemic antimycotic drugs (i.e. clotrimazole, fluconazole, ketoconazole, miconazole, tioconazole, amphotericin B). Compounds endowed with the lowest MICs underwent further testing in order to assess their cytotoxic effect (CC50) on Hep2 cells, which demonstrated their relative safety. Finally, QSAR and 3-D QSAR models were used to predict putative chemical modifications of the 1,3-thiazolidin-4-one scaffold in order to design new and potential more active compounds against Candida spp.

Keywords

3-D QSAR; Antifungal activity; Candida spp.; Cytotoxicity; Thiazolidinone.

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