Use of in-silico assays to characterize the ADMET profile and identify potential therapeutic targets of fusarochromanone, a novel anti-cancer agent

In Silico Pharmacology
Madison Wynne El-SaadiElahe Mahdavian

Abstract

For 30 years nature has provided a plethora of natural products with potential meaningful anti-cancer activity. Fusarochromanone (FC101a) is a small molecule fungal metabolite exhibiting potent in-vitro growth inhibitory effects and is capable of inducing apoptosis, suppressing angiogenesis and tumorigenesis, and inhibiting endothelial cell growth in multiple cancer cell lines. Despite all we know regarding FC101a, the mechanism of action and molecular target(s) of this compound have remained an enigma. Furthermore, modest in-vivo activity has been documented and requires addressing. Early stage pharmacokinetics (PK) assessment is vital to successful drug development. Herein, we aimed to use in-silico assays to i) characterize an in-depth ADMET profile of FC101a and ii) to probe for possible therapeutic targets. Two-dimensional SDF files of FC101a and 13 analogs were introduced into ADMET Predictor Version 7.1 that parses the structures in order to calculate molecular descriptors, which are used to estimate ADMET properties. Calculated ADMET values were analyzed and subjected to multiple drug-like indices, delivering a PK profile of each analog. To probe for possible targets, a total of 49 proteins were introduced into SYBYL-X ...Continue Reading

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Citations

Sep 29, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ming HongYibin Feng
Feb 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ming HongWeiwei Xing
Jan 10, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Jie LiChanggang Sun
Jan 17, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ahmad Husein AlkaffUsman Sumo Friend Tambunan
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vanessa Loaiza-CanoMarlen Martinez-Gutierrez

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Methods Mentioned

BETA
FACS
xenograft

Software Mentioned

TOX
Atom Expression View
GeomX
Risk
’ SYBYL - X
RCSB
SYBYL
Simulations
Tripos SYBYL - X
ADMET Predictor

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