Synthesis and Cytotoxic Activity of
Novel Metal Complexes Derived from Methyl-3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoate
as Potential CDK8 Kinase Inhibitors
posted on 2021-02-15, 13:38authored byAhmed Aboelmagd, Samir M. El Rayes, Mohamed S. Gomaa, Walid Fathalla, Ibrahim A. I. Ali, Mohamed S. Nafie, Faheem H. Pottoo, Firdos Alam Khan, Mohamed M. Ibrahim
Several metal complexes
of methyl-3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoate
derivatives were synthesized and tested for their anti-tumor activities.
The ligands include 3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoic
acid (1), 3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanehydrazide
(2), and 3-(4-chlorophenyl)-N′-(4-(dimethylamino)benzylidene)-3-hydroxy-2,2-dimethylpropanehydrazide
(3). The ligands were reacted with Cu (II), Ni (II),
and La (III) ions. The formed complexes were characterized using elemental
analysis (M%), molar conductivity in DMF (0.001 M), DTA, TG, FTIR,
ICP-AES, and magnetic susceptibility. The chemical structures of the
obtained complexes were interpreted, and their chemical formulas were
postulated. The anti-cancer activities of these complexes were examined
on human colorectal carcinoma cells (HCT-116) and also on normal cells
(HEK-293). The 48 h post treatments showed that out of 12 compounds,
10 compounds showed inhibitory actions on HCT-116 cells, whereas two
compounds did not show any inhibitory actions. Compounds 6c and 4a showed the highest inhibitory actions with IC50 = 0.154 and 0.18 mM and additionally compounds 3, 4b, and 6a with IC50 = 0.267,
0.205, and 0.284 mM, respectively.
All tested compounds did not show any inhibitory action on normal
HEK-293 cells. Molecular docking results provided a good evidence
for activity of the lead compounds 3 and 4a as CDK8-CYCC kinase inhibitors, which may proposed the mechanism
of action toward colon cancer therapy.