Romanian Society of Pharmaceutical Sciences
 

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HIPPURIC ACID-BASED OXADIAZOLE AND THIAZOLE DERIVATIVES: SYNTHESIS AND IN VITRO BIOLOGICAL EVALUATION

ALEXANDRA (BURLACU) PAVEL 1#, DIANA TATARCIUC 2#, MARIA DRĂGAN 3*, RODICA TATIA 4, ELENA-LĂCRĂMIOARA LISĂ 1, ANCUȚA IACOB (DINU) 1, CĂTĂLINA DANIELA STAN 3#, OANA MARIA DRAGOSTIN 1

1 Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, 800010, Galați, Romania
2 “Grigore T. Popa” University of Medicine and Pharmacy Iași, Department of I Internal Medicine, Faculty of Medicine, 700115, Iași, Romania
3 “Grigore T. Popa” University of Medicine and Pharmacy Iași, Department of II Pharmaceutical Science, Faculty of Pharmacy, 700115, Iași, Romania
4 Romanian National Institute of Research and Development for Biological Sciences, 060031, Bucharest, Romania

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Hippuric acid-based molecules were designed to explore oxadiazole and thiazole derivatives as dual antioxidant/antiproliferative chemotypes. Derivatives were obtained from hippuric acid via nitrile condensations and ring transformations, affording 1,2,4-oxadiazoles (10a - 10c) and thiazole (7) final compounds, alongside intermediates (3 - 5). Chemical structures were confirmed by Fourier transform infrared (FTIR) analyses, while antioxidant capacity was quantified by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reduction antioxidant power (FRAP) assays, using L-ascorbic acid as reference. Intermediates 3 - 5 were weak (DPPH, EC50 > 1500 µg/mL), whereas compounds 7 and 10a - 10c showed moderate activity across both assays (EC50 ~ 200 - 650 µg/mL). In vitro cytotoxicity, using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay (MTT) on Hep G2 and HT29 tumour lines, with NCTC fibroblasts for biocompatibility, indicated that compounds 7 and 10a - 10c produced the strongest growth-inhibitory trends, while maintaining comparatively lower effects on NCTC fibroblasts. Overall, these findings nominate hippuric acid-oxadiazoles and thiazole derivatives as tractable starting points for antitumor therapy optimisation. Future work will prioritise target selection, mechanism-oriented assays and integrated in silico/in vivo validation, to enhance potency and selectivity.