Kesic_2025_Eur.J.Med.Chem_287_117326

Herein, the modified synthesis of natural lactone (-)-cleistanolate (1) and its enantiomer (ent-1), along with the synthesis of six new analogues (3, 10, 11, 12, 13, ent-3), is presented. The antiproliferative activity of natural product 1 and its 22 analogues with lactone moiety was evaluated in vitro against eight human tumour cell lines and one normal cell line. SAR analysis revealed structural characteristics important for the activity of these types of compounds. The synthesized analogues are completely inactive toward the normal MRC-5 cell line. Their selectivity indexes (SI) range from 2.98 to 891.64. Furthermore, antimicrobial potential and inhibition of human acetyl- and butyrylcholinesterases of 1 and selected compounds have been evaluated.