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

Simone Carradori (Lead / Corresponding author), Bruna Bizzarri, Melissa D'Ascenzio, Celeste De Monte, Rossella Grande, Daniela Rivanera, Alessanda Zicari, Emanuela Mari, Manuela Sabatino, Alexandros Patsilinakos, Rino Ragno, Daniela Secci (Lead / Corresponding author)

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)274-292
Number of pages19
JournalEuropean Journal of Medicinal Chemistry
Volume140
Early online date19 Sep 2017
DOIs
Publication statusPublished - 1 Nov 2017

Fingerprint

hydrazine
Quantitative Structure-Activity Relationship
Candida
Scaffolds (biology)
Cytotoxicity
Scaffolds
Clotrimazole
Derivatives
Miconazole
Ketoconazole
Fluconazole
Chemical modification
Amphotericin B
Bioactivity
Safety
Molecules
Testing
Pharmaceutical Preparations
tioconazole

Keywords

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

Cite this

Carradori, Simone ; Bizzarri, Bruna ; D'Ascenzio, Melissa ; De Monte, Celeste ; Grande, Rossella ; Rivanera, Daniela ; Zicari, Alessanda ; Mari, Emanuela ; Sabatino, Manuela ; Patsilinakos, Alexandros ; Ragno, Rino ; Secci, Daniela. / 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. In: European Journal of Medicinal Chemistry. 2017 ; Vol. 140. pp. 274-292.
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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.",
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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. / Carradori, Simone (Lead / Corresponding author); Bizzarri, Bruna; D'Ascenzio, Melissa; De Monte, Celeste; Grande, Rossella; Rivanera, Daniela; Zicari, Alessanda; Mari, Emanuela; Sabatino, Manuela; Patsilinakos, Alexandros; Ragno, Rino; Secci, Daniela (Lead / Corresponding author).

In: European Journal of Medicinal Chemistry, Vol. 140, 01.11.2017, p. 274-292.

Research output: Contribution to journalArticle

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AU - Bizzarri, Bruna

AU - D'Ascenzio, Melissa

AU - De Monte, Celeste

AU - Grande, Rossella

AU - Rivanera, Daniela

AU - Zicari, Alessanda

AU - Mari, Emanuela

AU - Sabatino, Manuela

AU - Patsilinakos, Alexandros

AU - Ragno, Rino

AU - Secci, Daniela

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