Molecular Docking studies of Phytocompounds of Rheum emodi Wall with proteins responsible for antibiotic resistance in bacterial and fungal pathogens: In silico approach to enhance the bio-availability of antibiotics

Rheum emodi Wall. (Himalayan rhubarb) has been used to cure many human diseases. Literature survey demonstrated that it has many pharmacological activities such as antioxidant, antimicrobial, antiviral, anticancer and wound healing. The present study was aimed to understand if major phytocompounds of Rheum emodi could bind proteins responsible for antibiotic resistance in bacterial and fungal pathogens and enhance the potency of antibiotics. The major phytocompounds of R. emodi (emodin, rhein-13c6 and chrysophenodimethy ether) were retrieved from Pubchem and target proteins were retrieved from RCSB protein data bank. The docking study was performed with Hex 8.0.0 software and molinspiration, swiss ADME servers were used for determination of Lipinski rule of 5, drug-likeness prediction respectively, whereas, admetSAR and Protox-II tools were used for toxicity prediction. Among all the selected phytocompounds, emodin showed the best binding energy of -235.82 Kcal mol-1 and -245 Kcal mol-1 with cytochrome P450 14 alpha-sterol demethylase (PDB ID: 1EA1) and N-myristoyl transferase (PDB ID: 1IYL) receptors, respectively, which is more than that of fluconazole (-224.12 kcalmol-1 and -161.14 kcal mol-1). Similarly, with Penicillin binding protein 3 (PDB ID: 3VSL) receptor, emodin and Chrysophanol dimethyl ether showed highest binding energy of - 216.68 Kcal mol-1 and -215.58 kcal mol-1 which is comparable to erythromycin (-263.63 kcal mol-1), chloramphanicol (-217.34 kcal mol-1) and tetracycline (-263.63 kcal mol-1). All the selected phytocompounds also fulfill Lipinski rule, non-carcinogenic and non-cytotoxic in nature. These compounds also showed high LD50 value showing non-toxicity of these phytocompounds. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/086835v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@384d63org.highwire.dtl.DTLVardef@60d824org.highwire.dtl.DTLVardef@e23adorg.highwire.dtl.DTLVardef@485efe_HPS_FORMAT_FIGEXP M_FIG C_FIG