This paper describes the synthesis of new heterocycles from oxazol-5(4H)-one and 1,2,4-triazin-6(5H)-one classes containing a phenyl-/4-bromophenylsulfonylphenyl moiety. The oxazol-5(4H)-ones were obtained via condensation of 2-(4-(4-X-phenylsulfonyl)benzamido)acetic acids with benzaldehyde/4-fluorobenzaldehyde in acetic anhydride and in the presence of sodium acetate. The reaction of oxazolones with phenylhydrazine, in acetic acid and sodium acetate, yielded the corresponding 1,2,4-triazin-6(5H)-ones. The structures of the compounds were confirmed using spectral (FT-IR, ¹H-NMR, ¹³C-NMR, MS) and elemental analysis. The toxicity of the compounds was evaluated on Daphnia magna Straus crustaceans and on the budding yeast Saccharomyces cerevisiae. The results indicate that both the heterocyclic nucleus and halogen atoms significantly influenced the toxicity against D. magna, with the oxazolones being less toxic than triazinones. The halogen-free oxazolone had the lowest toxicity, and the fluorine-containing triazinone exhibited the highest toxicity. The compounds showed low toxicity against yeast cells, apparently due to the activity of plasma membrane multidrug transporters Pdr5 and Snq2. The predictive analyses indicated an antiproliferative effect as the most probable biological action. The PASS prediction and CHEMBL similarity studies show evidence that the compounds could inhibit certain relevant oncological protein kinases. These results correlated with toxicity assays suggest that halogen-free oxazolone could be a good candidate for future anticancer investigations.

This study presents the synthesis of novel heterocyclic derivatives from oxazol-5(4H)-ones and 1,2,4-triazin-6(5H)-ones classes containing the 4-chlorophenylsulfonylphenyl and arylidene motifs as potential bioactive molecules. The synthesis of new oxazol-5(4H)-ones was conducted by cyclocondensation of 2-(4-(4-chlorophenylsulfonyl)benzamido)acetic acid with several aromatic aldehydes. The reaction of oxazol-5(4H)-ones with phenylhydrazine afforded the new 1,2,4-triazin-6(5H)-ones. Spectroscopic techniques (IR, ¹H-, ¹³C-NMR, and MS) and elemental analysis were used to confirm the structures of all new compounds. The compounds were tested against Saccharomyces cerevisiae, and cells lacking the BLH1 gene were more susceptible to compound toxicity. Moreover, the compounds increased bleomycin toxicity against yeast cells. Structural similarity analysis against the ChEMBL database and approved drugs from DrugBank was performed to evaluate the structural novelty of the synthesized compounds and to obtain preliminary information regarding their potential pharmacological profiles.