الفهرس | Only 14 pages are availabe for public view |
Abstract The current study evaluated the cytotoxic activity of 11(4- Aminophenylamino) neocryptolepine (APAN), a novel analogue of the natural product alkaloid, neocryptolepine on MCF7 and A549 carcinoma cell lines as well as, the possible molecular mechanism through which it exerts its cytotoxic activity. The APAN was synthesized and characterized based on their spectral analyses. Scanning for anticancer target of the synthesized APAN by Swiss software indicated that APAN had the highest affinity for protein Aurora A kinase enzyme with affinity of about 60%. Furthermore, Super pred software was used to predict the possible indications for APAN. Molecular docking studies indicated that the binding affinity scores of APAN for protein protein data bank (PDB) code: 6C2T of Aurora A kinase recorded of −6.419 and Root mean square deviation (RMSD) value of 1.884 °A. Treatment of MCF7 and A549 cells with APAN induced cytotoxicity with IC50 of 2.35 and 4.34 μg /mL respectively. In addition, APAN significantly increased protein level of ANNEXIN V (apoptotic marker protein) in these cells. Furthermore, APAN significantly increased the protein expression of caspase 3 and P53. However, it significantly reduced the secretion of VEGF protein into the medium and decreased protein expression of PCNA and KI67 in MCF7 and A549 cells. This study indicated that APAN had cytotoxic activity against breast and lung cancer cell lines via increasing the expression of apoptotic proteins, caspase-3 and P53, and reducing the expression of proliferative proteins, VEGF, PCNA and KI67. |