2. Academic Validation
  3. Anti-Candida activity and cytotoxicity of a large library of new N-substituted-1,3-thiazolidin-4-one derivatives

Anti-Candida activity and cytotoxicity of a large library of new N-substituted-1,3-thiazolidin-4-one derivatives

  • Eur J Med Chem. 2016 Jan 1:107:82-96. doi: 10.1016/j.ejmech.2015.10.048.
Celeste De Monte 1,  Simone Carradori 2,  Bruna Bizzarri 1,  Adriana Bolasco 1,  Federica Caprara 1,  Adriano Mollica 3,  Daniela Rivanera 4,  Emanuela Mari 5,  Alessandra Zicari 5,  Atilla Akdemir 6,  Daniela Secci 1
Affiliations

Affiliations

  • 1 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
  • 2 Department of Pharmacy, "G. D'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy. Electronic address: simone.carradori@unich.it.
  • 3 Department of Pharmacy, "G. D'Annunzio" University of Chieti-Pescara, 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 Bezmialem Vakif University, Faculty of Pharmacy, Department of Pharmacology, Vatan Caddesi, 34093 Fatih, Istanbul, Turkey.
PMID: 26562544 DOI: 10.1016/j.ejmech.2015.10.048
Abstract

On the basis of the recent findings about the biological properties of thiazolidinones and taking into account the encouraging results about the Antifungal activity of some (thiazol-2-yl)hydrazines, new N-substituted heterocyclic derivatives were designed combining the thiazolidinone nucleus with the hydrazonic portion. In details, 1,3-thiazolidin-4-ones bearing (cyclo)aliphatic or (hetero)aromatic moieties linked to the N1-hydrazine at C2 were synthesized and classified into three series according to the aromatic or bicyclic rings connected to the lactam nitrogen of the thiazolidinone. These molecules were assayed for their anti-Candida effects in reference to the biological activity of the conventional topic (clotrimazole, miconazole, tioconazole) and systemic drugs (fluconazole, ketoconazole, amphotericin B). Finally, we investigated the selectivity against Fungal cells by testing the compounds endowed with the best MICs on Hep2 cells in order to assess their cell toxicity (CC50) and we noticed that two derivatives were less cytotoxic than the reference drug clotrimazole. Moreover, a preliminary molecular modelling approach has been performed against lanosterol 14-α demethylase (CYP51A1) to rationalize the activity of the tested compounds and to specify the target protein or Enzyme.

Keywords

Antimycotic effect; Candida spp.; Cytotoxicity; N-substituted thiazolidinones.

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