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

TY - JOUR

T1 - 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

AU - Carradori, Simone

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

N1 - Funding for this research was provided by: FILAS

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

KW - 3-D QSAR

KW - Antifungal activity

KW - Candida spp.

KW - Cytotoxicity

KW - Thiazolidinone

UR - https://www.scopus.com/pages/publications/85030121237

U2 - 10.1016/j.ejmech.2017.09.026

DO - 10.1016/j.ejmech.2017.09.026

M3 - Article

C2 - 28963991

AN - SCOPUS:85030121237

SN - 0223-5234

VL - 140

SP - 274

EP - 292

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -