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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Potential Biological Targets Prediction, ADME Profiling, and Molecular Docking Studies of Novel Steroidal Products from Cunninghamella blakesleana

Author(s): Maria Yousuf*, Sidra Rafi, Urooj Ishrat, Alekberzadeh Shafiga, Gulnara Dashdamirova , Vazirova Leyla and Heydarov Iqbal

Volume 18, Issue 2, 2022

Published on: 08 June, 2021

Page: [288 - 305] Pages: 18

DOI: 10.2174/1573406417666210608143128

Price: $65

Abstract

Background: New potential biological targets prediction through inverse molecular docking technique is another smart strategy to forecast the possibility of compounds being biologically active against various target receptors.

Objective: In this case of designed study, we screened our recently obtained novel acetylenic steroidal biotransformed products [(1) 8- β-methyl-14-α-hydroxyΔ4tibolone (2) 9-α-HydroxyΔ4 tibolone (3) 8- β-methyl-11- β-hydroxyΔ4tibolone (4) 6- β-hydroxyΔ4tibolone, (5) 6- β-9-α-dihydroxyΔ4tibolone (6) 7- β-hydroxyΔ4tibolone)] from fungi Cunninghemella Blakesleana to predict their possible biological targets and profiling of ADME properties.

Methods: The prediction of pharmacokinetic properties, membrane permeability, and bioavailability radar properties was carried out by using Swiss target prediction and Swiss ADME tools, respectively. These metabolites were also subjected to predict the possible mechanism of action along with associated biological network pathways by using Reactome database.

Results: All the six screened compounds possessed excellent drug ability criteria and exhibited exceptionally excellent non-inhibitory potential against all five isozymes of the CYP450 enzyme complex, including CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4. All the screened compounds are lying within the acceptable pink zone of bioavailability radar and showing excellent descriptive properties. Compounds [1-4 & 6] are showing high BBB (Blood Brain Barrier) permeation, while compound 5 is exhibiting high HIA (Human Intestinal Absorption) property of (Egan Egg).

Conclusion: In conclusion, the results of this study smartly reveal that in-silico based studies are considered to provide robustness towards a rational drug design and development approach; therefore, in this way, it helps to avoid the possibility of failure of drug candidates in the later experimental stages of drug development phases.

Keywords: Cunninghemella blakesleana, swiss target prediction, Swiss ADME, BOIELD-Egg pharmacokinetics, molecular docking, blood brain barrier (BBB), human intestinal absorption (HIA), reactome data-base, tibolone.

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