Synthesis and characterization of new mono and bis thiazolidine-2,4-dione derivatives

• Main Author: Tan, Glenn Kelly Uy
• Format: text
• Language: English
• Published: Animo Repository 2015
• Subjects: Pharmaceutical chemistry; Heterocyclic compounds; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/etd_masteral/5089
• Institution: De La Salle University

Mono and bis Thiazolidine-2,4-dione (TZD) derivatives (Ia, Ib, IVa, VII, VIIIa and VIIIc) with nonpolar moieties were synthesized and characterized. The synthesis of O-substituted TZD derivatives (Ib and VIIIc) involves the preparation of palkoxybenzaldehyde precursors (P1b and P8c) followed by condensation reaction with TZD. Compounds Ib and VIIIc were obtained in 47.55 and 12.58% yield respectively. The synthesis of TZD derivatives Ia, IVa, VII, and VIIIa involves the reaction of 5-(4-hydroxybenzylidene)thiazolidine-2,4-dione (A) with either alkyl halides or alkyl tosylates with varying lengths of nonpolar groups or linkers. This coupling reaction produced the target compounds Ia (5.78%), IVa (5.38%), VII (3.16%), and VIIIa (2.34%). The nonpolar moieties were incorporated to increase lipophilicity of the compounds and make the molecules better penetrate the cell membrane. Hopefully, this will lead to an increase in biological activity. Cytotoxic activity using PrestoBlue® assay were carried out on compounds Ia, Ib, IVa, VII, VIIIa and VIIIc against colorectal carcinoma (HCT-116), colorectal adenocarcinoma (HT-29), breast adenocarcinoma (MCF-7) and primary human dermal neonatal fibroblast (HDFn) cell lines. All compounds did not show cytotoxic activity in normal cells having no treatment concentration to inhibit at least 50% of the total number of HDFn cells unlike Bleomycin with an IC50 of 21.724 μg/mL. Compound Ib exhibited cytotoxic activity against HCT-116 (IC50: 23.711 μg/mL), HT-29 (IC50: 28.841 μg/mL)and MCF-7 (IC50: 31.303 μg/mL) cancer cell lines, which are comparable to Bleomycin (HCT-116, IC50: 28.237 μg/mL HT-29, IC50: 26.955 μg/mL MCF-7, IC50: 24.207μg/mL). Moreover, Ia and VII were comparable to Bleomycin against HCT-119 and HT-29 with IC50 values of 25.618 μg/mL and 32.259 μg/mL, respectively. These compounds may be potential candidates as an anti-cancer drug.