A Docking Study on Various Secondary Metabolites from W. somnifera on Tetrahydrodipicolinate N-Succinyltransferase Protein Involved in The Lysine Biosysnthesis Pathway in P. aeruginosa

Abstract

A crucial survival factor for leading pathogen (carrying 40-60% mortality rate) is Tetrahydrodipicolinate NSuccinyltransferase (DAPD EC 2.3.1.117) involves in lysine biosynthesis pathway of P. aeruginosa. Targeting the lysine biosynthesis pathway is a opportunistic and logical site to inhibit the effect of this organism. Withania somnifera, also known as “Indian ginseng”, a reputed herb in ayurvedic medicine, constituting various steroidal lactones (withanolides, withaferins) and saponins which shown various pharmacological activities. We described the docking of 11 secondary metabolites from Withania somnifera into the three dimensional structure of DapD protein of P. aeruginosa using swiss-dock server. Simultaneously, we have checked the ADME values and pharmacokinetics values of these secondary metabolites against the target protein. We have followed the “Lipnski rule of 5” principle and “Molinspiration” tool. Dihydowithaferin, 4-B, Hydroxywithanolide, Withanoloide E, Withanoloide F, Withanoloide D, Withanoloide A) have potential to be used as medicine to treat P.aeruginosa infections. Several known antibiotics also studied along with this approach for comparison purpose. Background/Objectives: Withania somnifera additionally referred to as “Ashwagandha” and “Indian ginseng” is a medicative plant constituting (isopelletierine, anaferine, cuseohygrine, and anahygrine, etc.), hormone lactones (withanolides, withaferins) and saponins., P.aeruginosa is a leading gram negative opportunist infectious agent, carrying a high 40-60% death rate and causes grievous infections in people with compromised immune systems. Tetrahydrodipicolinate N-Succinyltransferase (DAPD Europetwo.3.1.117) potential targets for brand spanking new antibacterial drug medication. Methods/Statistical analysis: The tying up method involves the prediction of matter conformation and orientation (or posing) inside a targeted binding web site. Swiss Dock may be a tying up internet server. All calculations are performed on the server aspect, so for tying up run’s don't need any machine power from the user. The ligands were neutralized and checked for his or her ADME properties victimization computer code Molinspiration obtainable at machine resources for Drug Discovery (CRDD). The secondary metabolites and antibiotics were conjointly subjected to Lipinski Rule of 5 value's on server The Supercomputing Facility for Bioinformatics & machine Biology (SCFBio), Indian Institute of Technology, N. Delhi. Findings: Among the eleven secondary metabolites from Withania somnifera and seven antibiotics we elect for docking, Ciproflaxin, Cephalosporin, Tobramycin, and Azlocillin showing the higher result compare to alternative compounds. Results of ADME properties showed Compounds as 4-B hydroxywithanolide, 2-3 dihydowitaferin A, Withanoloide E,Withanoloide D, Withanoloide A, and Withanoloide F has higher ADME values then the unremarkably used antibiotics (Azlocillin, Ciproflaxin, Ticarcillin, and antibiotic). Results of Lipinski rule of five values are given below in one table. Secondary metabolites like 4-B hydroxywithanolide, 2-3 dihydowitaferin A, Withanoloide E, Withanoloide D, and Withanoloide F showed higher results for Lipinski rule of five compare to antibiotics like Alocillin, Mefoxin, Meropenem, and Tobramycin. Improvements/Applications: Ashwagandha is employed from a few years for several treatments. This analysis additionally stresses the likelihood of this plant to use for cure of an added chronic infection. The experiment shows probabilities to develop a brand new drug.