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Virtual Screening of Natural Compounds as Potential PI₃K-AKT1 Signaling Pathway Inhibitors and Experimental Validation.

ABSTRACT: A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the computational analysis, i.e., ZINC2429155 (also named STL1) and ZINC1447881 (also named AC1), have been tested in an experimental assay, together with IQO as a positive control and quercetin as a negative control. Only STL1 clearly inhibited AKT activation negatively modulating the PI₃K/AKT pathway.

SUBMITTER: Dotolo S

PROVIDER: S-EPMC7831918 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Virtual Screening of Natural Compounds as Potential PI<sub>3</sub>K-AKT1 Signaling Pathway Inhibitors and Experimental Validation.

Dotolo Serena S Cervellera Carmen C Russo Maria M Russo Gian Luigi GL Facchiano Angelo A

Molecules (Basel, Switzerland) 20210118 2

A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the compu ...[more]

PMID: 33477701

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