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Table 5 Cancer cell growth inhibitory activity of compound 5o and
sunitinib toward sensitive (A-549) and resistant (NCI-H69AR) cell
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Compound No.
IC50 (µM)
A-549
Fold resistant
NCI-H69AR
5o
0.86 1.21
3.06
10.4 1.82
5.8 0.52
12.1
1.9
Sunitinib
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meeting the challenge of integrating chemotherapy and trastuzumab
(Herceptin). Semin Oncol. 2001;28(3):1–12.
Abbreviation: IC50, inhibitory concentration 50%.
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Detailed pharmacological studies were conducted on
compound 5o, a promising antiproliferative candidate, for
a better understanding of its pharmacological properties.
Compound 5o did not show any significant rise in caspase
3/7 activity at any concentration or time point tested.
Moreover, it exhibited an increase in the G1 phase and a
reduction in the S and G2/M phases of the cell cycle, and
it presented an IC50value of 10.4 μM toward the resistant
NCI-H69AR cancer cell line. Furthermore, the extent of
phosphorylated Rb protein was substantially decreased in
a dose-dependent fashion by compound 5o which was
further confirmed via Western blot analysis. This promotes
the assumption that inhibition of cyclin-dependent kinases
by compound 5o plays a role in its growth inhibitory
potential.
Overall, the current investigation indicates that the new
antiproliferative potential of the chemical entities 5a-w,
compound 5o in particular, can support the development
of new antiproliferative leads to be harnessed in preclinical
studies of cancer chemotherapy.
Acknowledgment
The authors would like to extend their sincere appreciation
to the Deanship of Scientific Research at King Saud
University for its funding of this research through the
Research Group Project no. RGP-196.
18. Anouar EH, Moustapha ME, Taha M, et al. Synthesis, molecular
docking and β-glucuronidase inhibitory potential of indole base oxa-
Disclosure
Dr Adam
B Keeton is a shareholder for ADT
Pharmaceuticals, LLC, outside the submitted work. Prof.
Dr. Gary A Piazza is a co-founder, shareholder, and Chief
Scientist for ADT Pharmaceuticals LLC and founder and
president of PDEi Pharmaceuticals LLC. The authors
report no other conflicts of interest in this work.
19. Attia MI, Witt-Enderby PA, Julius J. Synthesis and pharmacological
evaluation of pentacyclic 6a,7-dihydrodiindole and 2,3-dihydrodiin-
dole derivatives as novel melatoninergic ligands. Bioorg Med Chem.
20. Markl C, Attia MI, Julius J, et al. Synthesis and pharmacological
evaluation of 1,2,3,4-tetrahydropyrazino[1,2-a]indole and 2-[(phenyl-
methylamino)methyl]-1H-indole analogues as novel melatoninergic
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