In Silico Analog Design for Terbinafine Against Trichophyton rubrum: A Preliminary Study

Abstract

The diseases caused by dermatophytes are common among several other infections which cause serious threat to human health. It is evident that enzyme squalene epoxidase is responsible for prolonged dermatophyte infection and it is appealing to note that this enzyme is also responsible for fatty acid synthesis in these groups of fungi. In the present study, terbinafine drug which targets enzyme squalene epoxidase has been explored to design its various novel analogues. The present study suggests that many more prominent drug analogues could be constituted which may be crucial towards designing new drug candidates. In the present study, we have designed a series of such analogues viz. [(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalen-1-ylmethyl)amine, N-[8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]-2-(sulfoamino) acetamide, {[4-(dihydroxyamino)-8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]sulfanyl}methanol and (R)-{[4-({[(2E,6R)-6,7-dimethyloct-2-en-4-yn-1-yl](methyl)amino}methyl)-5-[(hydroxysulfamoyl)amino]naphthalen-1-yl]amino}sulfinic acid. Moreover, further by molecular docking approach the binding between enzyme and designed analogues was further analysed. The present preliminary report suggested a considerably good docking interaction score of -338.75 kcal/mol between terbinafine and squalene epoxidase from Trichophyton rubrum. This preliminary study implies that few designed candidate ligands can be effectual towards the activity of this enzyme and can play crucial role in pathogenesis control of T. rubrum.

An Alkaline Protease from Bacillus pumilus MP 27: Functional Analysis of Its Binding Model toward Its Applications As Detergent Additive

“…The protease from B. pumilus is quite stable in alkaline range, though a maximum of 8. The other researchers also reported where thermotolerant alkaline protease was active under comparable range of pH ( Banika and Prakash, 2004 ) and there are several reports on the optimization of enzymes, biological characterization of marine bacteria from Southern ocean, enzymatic applications, molecular modeling, bacterial platform technologies, systems biology approaches and gene editing tools which could be crucial toward improving the activity of enzyme and the industries now demand versatile proteases with activity at varied range of temperature ( Shukla and Gupta, 2007 ; Shukla et al, 2007 ; Baweja et al, 2015 ; Gupta and Shukla, 2015 , 2016a , b ; Gupta et al, 2015 ; Karumuri et al, 2015 ; Singh and Shukla, 2015 ; Kumar et al, 2016 ). Although, the thermophilic proteases are efficient stain removers but the trend is now shifting toward cold washing since it minimizes the energy during heat up process.…”

Molecular Characterization and Computational Modelling of New Delhi Metallo-β-Lactamase-5 from an Escherichia coli Isolate (KOEC3) of Bovine Origin

“…Prediction of ligand binding (docking) by in silico molecular docking is a useful approach to study molecular interactions [22]. This has been successfully applied for identification of novel antimicrobial targets [33], putative antifungal analogues [34]. However, limitations of computational docking should not be ignored while interpreting results [35].In the present study we employed computational docking for analysis of interactions between NDM-5 and five carbapenems antibiotics.…”

Molecular Modeling of Cloned Bacillus subtilis Keratinase and Its Insinuation in Psoriasis Treatment Using Docking Studies

“…Docking score and energy of the complexes are represented in Table 1. Molecular docking is generally used to learn the drug-receptor interaction to envisage the affinity and activity of the small molecule to their protein [20]. The model energy score (E-model) which combines the glide score, the excess internal energy and non bonded interaction energy of the generated ligand conformation and the glide score were used to rank the docked conformation of the ligands with the protein (fig.…”