Anti-inflammatory activity and cytotoxicity against ovarian cancer cell lines by amide alkaloids and piperic esters isolated from Piper longum fruits: In vitro assessments and molecular simulation

Three new amide alkaloids, piperlongumamides D-F (14 , 19 , and 32); a new piperic ester, piperlongumester A (45); and two new natural compounds, methyl (2E,4Z)-5-(1,3-benzodioxol-5-yl)penta-2,4-dienoate (46) and trans-piperolein B ester (47), along with 41 known compounds were isolated from the fruits of Piper longum L. Their structures were identified by analyzing spectroscopic data, including mass spectrometry, 1D, and 2D NMR data. The anti-inflammatory and cytotoxic activities of all isolated compounds (1-47) were evaluated. Com-pounds 3 , 6 , and 19 inhibited nitric oxide production with IC50 values of 16.1 +/- 0.94, 14.5 +/- 0.57, and 27.3 +/- 1.11 mu M, respectively, whereas compound 1 exhibited strong cytotoxic activity toward three ovarian cancer cell lines A2780, TOV-112D, and SK-OV3, with IC50 values of 6.7 +/- 0.77, 5.8 +/- 0.29, and 48.3 +/- 0.40 mu M, respectively. Molecular docking simulations were performed to identify the interaction and binding mechanisms of these active metabolites with proteins related to inflammation and cancer.

Automated summary

Five new compounds were isolated from the fruits of Piper longum L., along with 41 known compounds. The anti-inflammatory and cytotoxic activities of all isolated compounds were evaluated, and several compounds showed significant activity. Molecular docking simulations revealed the interaction and binding mechanisms of these active metabolites with proteins related to inflammation and cancer.