Abstract
ADMET predictions indicate good drug like properties.
Compound 4i could serve as a potential hit candidate.
Further structural optimization might give novel anticancer therapeutics.
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•Design and synthesis of novel amide conjugates of pyrimidin-4-one.•in vitro antiproliferative evaluation of the synthesized compounds.•Compound 4i elicited significant anti-proliferative activity.•Showed growth percent of 1.93 against the breast tumor cell line T-47D.•It also inhibited the growth of CNS tumor cell line SNB-75 by 86%•Compound 4i found to inhibit GSK-3β with IC50 value of 71 nM.
A new series of novel amide conjugates of pyrimidin-4-one and aromatic/heteroaromatic /secondary cyclic amines has been synthesized and their in vitro antiproliferative activities against a panel of 60 human cancer cell lines of nine different cancer types were tested at NCI. Among the synthesized compounds, compound (4i) showed significant anti-proliferative activity. Compound (4i) displayed most potent activity against the breast tumor cell line T-47D and CNS tumor cell line SNB-75 exhibiting a growth of 1.93 % and 14.63 %, respectively. ADMET studies of the synthesized compounds were also performed and they were found to exhibit good drug like properties. Compound (4i) was found to exhibit potential inhibitory effect over GSK-3β with IC50 value of 71 nM. The molecular docking studies revealed that (4i) showed good binding affinity to GSK-3β and revealed multiple H-bonding and p-cation interactions with important amino acid residues on the receptor site. Compound (4i) may thus serve as a potential candidate for further development of novel anticancer therapeutics.