RESUMEN
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-ß-methyl-14-α-hydroxyΔ4tibolone (2) 9-α-HydroxyΔ4 tibolone (3) 8-ß-methyl-11-ß-hydroxyΔ4tibolone (4) 6-ß-hydroxyΔ4tibolone, (5) 6-ß-9-α-dihydroxyΔ4tibolone (6) 7-ß-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.
Asunto(s)
Cunninghamella , Barrera Hematoencefálica , Diseño de Fármacos , Humanos , Absorción Intestinal , Simulación del Acoplamiento MolecularRESUMEN
Abstract Ananas Comosus (also known as pineapple) is a part of Bromeliaceae family and it is consumed as food as well as folk medicine for the treatment of various diseases. It is reported that pineapple is a rich source of bromelain, a cysteine protease and it is considered as an important enzyme in different industries due to its significant therapeutic and industrial applications such as anticancer, anti-inflammatory and meat tenderizing. Bromelain is mostly present in fruit and stem of pineapple, but it is reported that crown, core, and peels, which constitute the waste of the pineapple plant, also contain bromelain but limited data is available. Therefore, the proposed study aimed at utilizing pineapple waste for the extraction and characterization of bromelain. Firstly, crude bromelain was extracted with phosphate buffer (pH 7), then it was subjected to partial purification using different fractions of ammonium sulphate (NH4)2SO4 such as 30, 40, 50 and 60% followed by desalting and concentration. Enzyme activity was calculated by using casein digesting unit (CDU) method. The results demonstrated that the crown bromelain showed highest purification of 4.34-fold at 30% (NH4)2SO4 saturation, whereas core and peel bromelain showed highest purification of 2.75 and 2.59-fold at 40% (NH4)2SO4 saturation. The molecular weight of crude and partially purified bromelain was determined by SDS-PAGE analysis and found to be 26 KDa. The pH and thermal stability of all the parts of pineapple showed maximum stability at pH 7 and at 35oC temperature.