Synthesis of ring-A serjanic acid derivatives and their cytotoxic evaluation through the brine shrimp lethality assay (BSLA)

Abstract

Abstract Sixteen serjanic acid derivatives were synthesized by modification of the A-ring of the triterpenoid skeleta. Fischer indolization of intermediate 2 with the requisite aromatic hydrazines afforded the indolo-triterpenes 8–13. Also, reaction of 2 with hydroxylamine hydrochloride in pyridine provided the desired C-3 oxime 14, while pyrazine 15 was obtained by condensation of 2 in the presence of ethylenediamine and sulphur in morpholine. Finally, the Claisen-Schmidt condensation of intermediate 2 with corresponding substituted benzaldehydes 16–23, afforded benzylidine ketones 24–31. All compounds were elucidated on the basis of NMR and HR-MS spectroscopic data and evaluated for their in-vitro cytotoxicity to the Brine Shrimp Lethality Assay (BSLA). As a result, the compounds exhibited medium to good cytotoxic potential and this activity was as high as eight times that of serjanic acid (1) on the tested zoophytes.