TITLE:
Development of Novel Benzimidazole Derivates as Potent and Selective Akt Kinase Inhibitors Using In-silico Approaches
AUTHORS:
Rasha Ghanem Kattoub, Faten Sliman, Mohammad Kousara
KEYWORDS:
Akt, Selective ATP-competitive Inhibitors, Benzimidazole, Molecular Docking, In-silico ADMET
JOURNAL NAME:
International Journal of Organic Chemistry,
Vol.11 No.3,
September
26,
2021
ABSTRACT: The serine/threonine Akt kinase signaling pathway
plays an essential role not only in tumorigenesis but also in the potential
response to anticancer therapeutic agents. Therefore, aiming to identify potent
and selective Akt inhibitors, a novel series of benzimidazole derivatives were designed and docked within the crystal structure of Akt1 kinase. In
order to predict their selectivity, the hit compounds were docked against the
protein kinase A (PKA), which is the closely related AGC family kinase protein.
Moreover, in-silico ADMET-related descriptors were estimated to predict the pharmacokinetic
properties for the selected compounds. Among the designed molecules, four
compounds were found to have the best binding affinity and good selectivity to
Akt1 kinase, furthermore, those compounds had acceptable ADMET properties and were predicted to be non-mutagenic, which could account them as promising Akt1
inhibitory agents for further investigations.