Abstract

Phytochemical investigation of the methanol extract of the seeds of P. harmala afforded two new alkaloids namely, 1‑hydroxy-1-norharmaline (4) and 7-norharmalacidine hydrochloride (5) and a new semisynthetic derivative, 1,2-diacetyl-1-nor-harmaline hydrochloride (2Ac/4Ac). Additionally, four known derivatives viz., harmine (1), harmalacidine hydrochloride (2), harmaline hydrochloride (3), and harmaline (3AB) were identified. The structures of these compounds were elucidated using NMR, HR-ESIMS, and FTIR spectroscopy. Compounds 3 and 2Ac/4Ac showed the maximum in vitro COX-2 inhibition (IC50 2.638 and 9.294 μM, respectively), whereas remarkable 5-LOX inhibition was recorded for 3, 3AB, 4, and 2Ac/4Ac (IC50 1.63, 4.596, 6.174, and 3.237 μM, respectively). Docking studies showed the ability of 2 and 2Ac/4Ac to establish H-bonds with the crucial residues, Tyr385, Tyr355, and Arg120 of COX-2 enzymes. Also, compounds 2, 4, 5, and 2Ac/4Ac showed the ability to coordinate with the iron metal in 5-LOX. Our results suggested β-carboline alkaloids as promising leads for developing new anti-inflammatory drugs.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call