In this work, the natural piperine moiety was utilised to develop two sets of piperine-based amides (
5a–i
) and ureas (
8a–y
) as potential anticancer agents. The anticancer action was assessed against triple negative breast cancer (TNBC) MDA-MB-231, ovarian A2780CP and hepatocellular HepG2 cancer cell lines. In particular,
8q
stood out as the most potent anti-proliferative analogue against TNBC MDA-MB-231 cells with IC
50
equals 18.7 µM, which is better than that of piperine (IC
50
= 47.8 µM) and 5-FU (IC
50
= 38.5 µM). Furthermore,
8q
was investigated for its possible mechanism of action in MDA-MB-231 cells
via
Annexin V-FITC apoptosis assay and cell cycle analysis. Moreover, an in-silico analysis has proposed VEGFR-2 as a probable enzymatic target for piperine-based derivatives, and then has explored the binding interactions within VEGFR-2 active site (PDB:4ASD). Finally, an
in vitro
VEGFR-2 inhibition assay was performed to validate the
in silico
findings, where
8q
showed good VEGFR-2 inhibitory activity with IC
50
= 231 nM.
Introduction: Cancer is a large group of disorders characterized by uncontrolled cellular proliferation. It is one of the most devastating diseases all over the world. Recently, there is an increased interest in the clinical use of natural products as a safe, efficient, and economic therapeutic alternative. Honey bee products therapy, apitherapy, was used to control various diseases including cancer. Objectives: The primary objective of this study was to screen potential cytotoxic effects of honey bee products against different cancer types. Materials and Methods: Samples of honey, venom and propolis were collected from different Egyptian localities with different techniques and tested by MTT cell-based assay against liver (HeP-G2), breast (MCF-7), and colorectal (Caco-2) cancer cell lines. Results: The results showed that, Italian dissected method-bee venom was the most active among all the tested samples against Hep-G2 (93.92%), Caco-2 (93.92%) and MCF-7 (90.17%). However, Libyan propolis proved to be most active among all tested propolis samples. On the other hand, all tested honey samples showed non-remarkable activities except Asyut-clover honey (49.84% against Caco-2 cell line). Conclusion: The results showed that, bee venom, propolis and honey are interesting agents that have valuable activities against Hep-G2, Caco-2 and MCF-7 with bee venom being the most effective agent that might be incorporated in cancer remedy regimens after further studies.
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