In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica
Open Access
- 12 May 2022
- Vol. 11 (10), 1295
- https://doi.org/10.3390/plants11101295
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.Keywords
Funding Information
- Deanship of Scientific Research at Jouf University (DSR-2021-01-0102)
This publication has 41 references indexed in Scilit:
- c-Jun-mediated anticancer mechanisms of tylophorineCarcinogenesis: Integrative Cancer Research, 2013
- Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletionMolecular Cancer, 2013
- Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophora indica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2–mediated angiogenesisMolecular Cancer, 2013
- A new phenanthroindolizidine alkaloid from Tylophora indicaChemical Papers, 2013
- Cancer and Radiation Therapy: Current Advances and Future DirectionsInternational Journal of Medical Sciences, 2012
- Phenanthrene-Based Tylophorine-1 (PBT-1) Inhibits Lung Cancer Cell Growth through the Akt and NF-κB PathwaysJournal of Medicinal Chemistry, 2009
- Natural products and drug discoveryEMBO Reports, 2009
- Antitumor Agents 252. Application of validated QSAR models to database mining: discovery of novel tylophorine derivatives as potential anticancer agentsJournal of Computer-Aided Molecular Design, 2007
- Solvent effects in the structure dereplication of caffeoyl quinic acidsMagnetic Resonance in Chemistry, 1999
- The pathogenesis of cancer metastasisNature, 1980