Potential Biological Targets Prediction,
BOIELD-Egg pharmacokinetics
Cunninghemella blakesleana
Swiss ADME
blood brain barrier (BBB)
human intestinal absorption (HIA)
molecular docking
reactome data-base
swiss target prediction
tibolone
Journal
Medicinal chemistry (Shariqah (United Arab Emirates))
ISSN: 1875-6638
Titre abrégé: Med Chem
Pays: Netherlands
ID NLM: 101240303
Informations de publication
Date de publication:
2022
2022
Historique:
received:
20
10
2020
revised:
07
01
2021
accepted:
26
01
2021
pubmed:
10
6
2021
medline:
27
1
2022
entrez:
9
6
2021
Statut:
ppublish
Résumé
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. 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. 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. 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). 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.
Sections du résumé
BACKGROUND
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
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 34102986
pii: MC-EPUB-116042
doi: 10.2174/1573406417666210608143128
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
288-305Subventions
Organisme : Higher Education Commission, Pakistan
ID : 106-2333-PS6-138
Informations de copyright
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