In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica

Abstract

The phenanthroindolizidine alkaloid (-)-tylophorine has been reported for its significant anticancer activity working through different biomechanistic pathways. The current study aimed to evaluate the anticancer activity of phenanthroindolizidine alkaloids isolated from Tylophora indica. Six phenanthroindolizidine alkaloid (compounds 1–6) in addition to septicine (7), chlorogenic acid (8), and chlorogenic acid methyl ester (9) were isolated from Tylophora indica using different chromatographic techniques including vacuum liquid chromatography (VLC) and preparative high performance liquid chromatography (HPLC). The isolated compounds structures’ were determined using various spectro-analytical techniques, i.e., 1H-NMR, 13C-NMR, and mass spectrometry. The isolates’ structural stereochemistry and structural geometries were determined with the help of chiroptical techniques together with comparisons with the available standard samples. The in vitro anti-proliferative activity on three different cell lines, MCF-7, HepG2, and HCT-116 were evaluated. Among all the isolated compounds, tylophorinidine (5) was the most active cytotoxic agent with the lowest IC50 values at 6.45, 4.77, and 20.08 μM against MCF-7, HepG2, and HCT-116 cell lines, respectively. The bioactivities were also validated by the in vitro kinase receptors inhibition assay. Compound (5) also exhibited the highest activity with lowest IC50 values (0.6 and 1.3 μM against the Aurora-A and Aurora-B enzymes, respectively), as compared with all the isolated alkaloidal products. The structure activity relationship on the molecular properties, molecular attributes, and bioactivity levels were analyzed, interrelated, and the molecular docking studies on two different receptors, Aurora-A and Aurora-B, were determined, which provided the confirmations of the bioactivity with receptor-ligand geometric disposition, energy requirements, lipophilicity, and detailed the binding pharmacophore involvements responsible for bioactivity elicitations.

Phenanthroindolizidine Alkaloids Isolated from Tylophora ovata as Potent Inhibitors of Inflammation, Spheroid Growth, and Invasion of Triple-Negative Breast Cancer

“…Nevertheless, in silico docking studies postulate kinase inhibition through binding to the ATP-binding site as a pharmacological mode of action for PAs. Studies by Liu et al report the blocking of AKT for another epimer of compound ( 1 ), namely HTBP1 [ 87 ], and Mostafa et al showed blocking of Aurora A and B kinases for tylophorinine and for ( 2 ) [ 89 ]. However, to date, the function of kinase inhibition by PAs is unclear for breast cancer.…”

“…In contrast, proliferation blocking by PAs might rely on inhibiting checkpoint proteins in the cell cycle or by inhibiting DNA replication. Recently, Aurora A and B kinases were found as novel targets for tylophorinine and for ( 2 ) at a low micromolar concentration in MCF7 [ 89 ]. As a direct substrate, p53 is phosphorylated and subsequently degraded [ 95 ].…”

Medicinal Plants: Advances in Phytochemistry and Ethnobotany

“…Merr, an Indian native species, was described by Mostafa et al (2022). The compound presented IC 50 values of 6.45, 4.77, and 20.08 µM in MCF-7, HepG2, and HCT-116 cell lines, respectively [12]. The in vitro cytotoxic and anti-migratory effects of extracts from Marantodes pumilum Blume Kuntze, a Malaysian plant, as well as of an isolated compound from the chloroform fraction, 5-henicosene-1-yl-resorcinol, on prostate cancer cells (PC3) was shown by Hanafi et al (2023).…”