Evaluation of anti-tuberculosis activity in selected vegetable crops: Garlic, Onion and Drumstick

Abstract

Tuberculosis (TB) is the second worldwide killer infectious disease caused by Mycobacterium tuberculosis (TB). Globally it kills 1.8 million people annually and 40,000 from India. Current TB treatment is based on principles of combination chemotherapy which takes prolonged period. Most of the anti-TB drugs are good old discoveries and now they are resistant to new strains of TB. The emergence of multi drug resistant (MDR) and extensively drug resistant (XDR) mutants and the adverse effect to immune system in patients co-infected with HIV are the major hurdles in the TB treatment. Thus the discovery of new vaccines and novel drugs become the need of the hour. History shows the practice of several herbal combinations that have been using traditionally from the ancient civilizations against tuberculosis. Many indigenous vegetable crops of Kerala are having anti-TB properties but its efficacies and the pharmacological action are not yet scientifically investigated. In the present study the phytomolecules reported from Allium cepa, Allium sativum and Moringa oleifera were screened through in silico methods. Decaprenylphosphoryl-beta-D-ribose epimerase (DprE1) protein was selected as the target molecule for doing the in silico docking analysis. DprE1 is an enzyme responsible for the synthesis of arabinan, the virulent factor in Mycobacterium, tuberculosis. The 3-D structure of the molecule was retrieved from PDB (PDB id 4FDO) and the active site DprE1 was detected using the tool PDBsum. Information regarding the chemical molecules reported in the selected spices was collected through literature survey and databases. A total of 175 phytochemicals (Allium cepa – 81, Allium sativum – 52 and Moringa oleifera – 42) were screened. The selected phytochemicals were docked against DprE1 protein using AutoDock 4.2. The docked structures having ΔGbind ≤ -5 kcal/mol-1 were selected as best hit molecules. To nullify the errors in lead identification the top ranked hit molecules were again docked using the tools Hex server, iGEMDOCK, FireDockand SwissDock. The docked results were statistically analyzed following DST and Zhang rule and selected the top ranked molecules viz. 24-Methylenecycloartanol (A.cepa), Kaempferol & Quercetin (A. sativum & M. oleifera) and 4-hydroxymellein from M. oleifera. All the four compounds have been subjected for bioactivity and druglikness score using Molinspiration and MolSoft tools. The ADMET property study was done by using the tool pkCSM. Kaempferol, Quercetin and 4-hydroxymellein showed acceptable range in both bioactivity analysis and in ADMET property prediction. Overall study substantiate that Moringa stands first in the evaluation as it produce all the three sought out leads followed by garlic with two leads. Theoretical prediction of drug likeliness only gives probability and its activity in a biological system. Therefore, in vitro & in vivo studies and in-depth clinical trials are necessary for developing a drug out of the lead molecules.