Novel hydantoin derivatives: Synthesis and biological activity evaluation

Abstract

Novel compounds derived from hydantoin were synthesized using a chloroacetyl chloride linker in conjunction with terminal compounds of sulphonamides and amines. The compounds were subjected to various analytical techniques, including LC-MS/MS, 1H NMR, 13C NMR, FT-IR, and determination of melting point. Subsequently, the synthesized compounds were evaluated for their potential anti-cancer properties (against) breast cancer (MCF-7) and lung cancer (A549) cell lines by the MTT assay. Additionally, the compounds' anticonvulsant activity was assessed using pentylenetetrazol (PTZ)-induced seizure in mice. Furthermore, the inhibitory activity of selected compounds against the PI3Kα enzyme at a concentration of 100 µM was investigated. The biological evaluation of the compounds did not show the expected anticonvulsant effect when tested at various doses (5, 10, and 20 mg/kg b.w using the intraperitoneal injection), with all mice showing a seizure score of 5. MTT assay showed moderate anti-cancer activity against, the (A549) cell line, with compound 37 exhibiting the highest inhibition of cell viability at 55.1%. In the case of the breast cancer cell line, compounds 37, 40, 42, and 45 demonstrated inhibition percentages ranging from 64% to 74%. Moreover, the compounds displayed a relatively limited inhibitory effect on PI3Kα activity during the in-vitro evaluation compared to staurosporine. These findings suggest that further optimization and modification of the synthesized compounds may be necessary to enhance their anticonvulsant and anti-cancer properties, particularly regarding PI3Kα inhibition.

Keywords

• Synthetic hydantoin derivatives
• Sulfonamide
• Amine
• Anticonvulsants
• Anti-cancer
• PI3Kα