New Bioactive Esters and Phosphonates Semisynthesized From (±)-Vasicinone: An Alkaloid Isolated FromPeganum harmala

Abstract

A series of N-tosyl α-amino acids 2a-e, prepared using a tosyl chloride protecting group, was condensed with (±)-vasicinone 1, isolated from the seeds of the plant Peganum harmala, to generate the corresponding esters 3a-e and 3b′-e′. (±)-Vasicinone 1 was also reacted with chloroacetic acid chloride to afford a new chlorinated ester 4 which was refluxed with trialkyl phosphites to give 2 new phosphonates 5a,b. All synthesized compounds were characterized with the help of spectroscopic means, including NMR (1H,13C, and31P) and ES-HRMS, and then screened for their in vitro anti-acetylcholinesterase (AChE), anti-5-lipoxygenase (5-LOX), and cytotoxic activities (MCF-7, OVCAR-3, and HCT-116 cell lines). Most synthesized derivatives exhibited a cytotoxic activity against 3 cell lines used. The phosphonate derivative 5b was found to be the most active one (IC50= 63.7 ± 1.4 µM) against AChE enzyme. Only 2 diastereoisomers 3e and 3e′ exhibited activity against 5-LOX enzyme with IC50values of 63.1 ± 4.2 and 79.2 ± 8.3 µM, respectively.