الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 134 |  |  |
| | | from | 134 | | |
Abstract
The current study evaluated the cytotoxic activity of 11-(1,4-
Bisaminopropylpiperazinyl) neocryptolepine (BAPPN), a novel analogue of the
natural product alkaloid, neocryptolepine, on hepatocellular carcinoma (HepG2)
and colon carcinoma (HCT-116) cell lines, as well, the possible molecular
mechanism through which it exerts its cytotoxic activity. BAPPN was
synthesized and characterized with FT-IR and NMR spectroscopic. The binding
affinity scores of BAPPN for caspase-3 PDB: 7JL7 was −7.836, with an RMSD
of 1.483◦ A. InsilIco screening of ADME properties indicated that BAPPN
showed promising oral bioavailability records in addition to their high
gastrointestinal absorption and blood–brain barrier penetrability. Treatment of
HepG2 and HCT-116 cells with BAPPN induced cytotoxicity with IC50 of 3.3
μg/ml for HepG2 cells and IC50 of 23μg /mL for HCT-116 cells. In addition, it
induced cell injury and morphological changes in ultracellular structure
including, cellular delayed activity, vanishing of membrane blebbing, microvilli,
cytoplasmic condensation, and shrunken nucleus with more condensed
chromatin autophagosomes. Moreover, BAPPN significantly increased protein
expression of Annexin V (apoptotic marker protein) in these cells. Furthermore,
BAPPN significantly increased the protein expression of casepase-3 and tumour
suppressor protein (P53). However, it significantly reduced the secretion of
vascular endothelial growth factor (VEGF) protein into the medium and
decreased protein expression of proliferation cellular nuclear antigen (PCNA)
and KI67 in HepG2 and HCT-116 cells. This study indicated that BAPPN had
cytotoxic action via upregulation of apoptotic proteins against liver and colon
cancer cell lines, caspase-3 and P53, and downregulation the expression of
proliferative proteins, VEGF, PCNA and KI67.