In vitro and in silico inhibition of COX-2 and 5-LOX by beta-carboline alkaloids from the seeds of Peganum harmala L.

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 iden-tified. 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 9.294mM, respec-tively), whereas remarkable 5-LOX inhibition was recorded for 3, 3AB, 4, and 2Ac/4Ac (IC50 1.63, 4.596, 6.174, and 3.237 mM, 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 ,B-carboline alkaloids as promising leads for developing new anti-inflammatory drugs.(C) 2022 SAAB. Published by Elsevier B.V. All rights reserved.

Automated summary

Phytochemical investigation of the methanol extract of P. harmala seeds led to the discovery of two new alkaloids and a new semisynthetic derivative, as well as the identification of four known derivatives. These compounds exhibited anti-inflammatory activity and interacted with key residues of specific enzymes.