Introduction
Tuberculosis continues to be the global public health threat. It is therefore imperative to find a novel antitubercular drug target that is unique to the structural machinery or is essential to the growth and survival of the bacterium. Mycolyl–arabinogalactan–peptidoglycan (mAGP) complex is the cell wall core made up of proteins, peptidoglycan, arabonogalactan and mycolic acid. It is a very attractive target for drug development against tuberculosis.1 Enoyl-acyl carrier protein reductase (ENR) is a key enzyme of the type II fatty acid synthesis (FAS) system. ENR is an attractive target for narrow spectrum antibacterial drug discovery because of its essential role in metabolism and its sequence conservation across many bacterial species. In addition, the bacterial ENR sequence and structural organization are distinctly different from those of mammalian fatty acid biosynthesis enzymes.2, 3, 4 Isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin are the current drug treatment available presently. In developing countries, the Incidence of TB remains high and global threat is multi drug resistant. New anti-TB drugs that can shorten the treatment regimen and/or target the resistant TB strains are urgently needed.
Numerous medicinal floras are available all over the world. Medicinal plants are age long agents for human beings as they were having much therapeutic value. Plants are playing an important role in drug extraction and are economically critical. They contain many constituents which can be beneficial as remedy for many human sicknesses. Some plant extracts are also used to avoid the antibiotic resistance.5
Couroupita guianensis Abul have its place in the family lecythidaceae, habitually known as cannonball tree, Sal tree or Ayahuma tree and vernacular name varies according to the different places. Traditionally, it shares its importance in treatment of animals. It is augmented with a quantity of active component like isatin, linalool, eugenol, farnesol, beta sitosterol, nerol, linoleic acid, benzyl alcohol, 7 methoxy 4-methyl coumarin, quercitin, terpineol, trypthantrin, indirubin, benzthiazole, indigo, hexadecanoic acid, limonene, alpha amyrin, beta amyrin, beta amyrin palmitate, stigmasterol, campesterol, beta carotene. The extracts of Couroupita guianensis shows a variety of pharmacological activities. In addition, chemical diversity of secondary plant metabolites that result from plant evolution may be equal or superior to that found in synthetic combinatorial chemical libraries.
One such important medicinal plant is Couroupita guianensis. The parts of this tree have a lot of medicinal properties, which are traditionally used by the people. Given below are the details of the plant.
Like other fruits and vegetables, C. guianensis is also a rich source of antioxidants and thus can help to prevent degenerative diseases. Different parts of this plant have been traditionally used in the folk medicine for healing various diseases. Umachigi et al., has provided a scientific rationale for the traditional use of C. guianesis in the management of skin diseases such as sores, boils and itching. The infusions prepared from the leaves, flowers, and barks of C. guianensis are used for the treatment of hypertension, tumours, pain, and inflammatory processes.
Secondary metabolites such as phenols and flavonols exist widely in plants and are considered as important dietary antioxidants, which are responsible for the prevention of consequences of oxidative stress in biological system Similarly, Elumalai et al., have reported the presence of secondary metabolites in the leaves of Couroupita guianesis which might be responsible for its potential antioxidant, anti-arthritic and anti platelet activities.6
Materials and Methods
Ligand preparation
3D chemical structure of selected bioactive compounds such as isatin, eugenol, farnesol, beta sitosterol, nerol, benzyl alcohol, trypthantrin, indirubin, indigo, alpha amyrin, beta amyrin, stigmasterol, campesterol were downloaded from PubChem database in sdf format:
Protein preparation
3D crystalline structure of protein [PDB ID is 4TZK] was acquired from protein data bank: It was prepared using prep wizard of glide software. Crystal structure of Mycobacterium tuberculosis enoyl reductase (INHA) complexed With 1-Cyclohexyl-N-(3,5-Dichlorophenyl)-5-Oxopyrrolidine-3-Carboxamide. The organism is Mycobacterium tuberculosis H37Rv. Its X ray diffraction has resolution of 1.62 A. It is an enzyme with A chains. Grid was generated using the glide grid generation wizard.
Ligand docking
It was performed using ligand docking –Glide.
Analysis of docked complex7
Table 1
Docking score and hydrogen bond interaction.
Results and Discussion
Betasitosterol had hydrophobic interaction with the target and one hydrogen bond. The OH of sterol nucleus formed a hydrogen bond with ILE 194. OH of campesterol formed a hydrogen bond with THR 196.Trypanthrin had hydrophobic interaction and Pie-Pie stacking with PHE 149 and TYR 158. Beta-amyrin had hydrophobic interaction and one hydrogen bond with ILE 194. Alpha amyrin had hydrophobic interaction. The carbonyl oxygen of Coup had hydrogen bond with ILE 194. Coup had Pie-Pie tacking with TYR 158 and hydrophobic interaction. Coup 2, indirubin, and Decasanoic acid had hydrophobic interaction. Indigo had hydrophobic interaction, Pie-Pie stacking with PHE 149 and Pi – cation interaction with LYS 165. Farnesol had hydrophobic interaction and one hydrogen bond with TYR 158. Calotroponaphthalene had hydrophobic interaction, pie-pie stacking with PHE 41 and water molecule formed a hydrogen bond with PHE 41 and oxygen of OCH3 of calotroponaphthalene. Benzyl alcohol had hydrophobic interaction, Pie-Pie stacking with PHE 149 and OH of it formed hydrogen bond with ILE 194.
Eugenol had hydrophobic interaction, Pie-Pie stacking with PHE 41 and formed hydrogen bond. The OH of eugenol formed hydrogen bonds with VAL 65 and LEU 63. Isatin had hydrophobic interaction, pie-pie stacking with PHE 41 and hydrogen bonds with target. The NH of isatin formed hydrogen bond with ASP 64 and carbonyl oxygen nearer to NH formed hydrogen bond with VAL 65. The OH of nerol had hydrogen bond interaction with THR 39.
The standard isoniazide had hydrophobic interaction, Pie-Pie stacking with PHE 41 and hydrogen bonds. The NH2 of isoniazide formed hydrogen bond with GLY 96 and N in the pyridine ring formed hydrogen bond with VAL 65.The validation is performed and had docking score of – 14.96.It had eight hydrogen bond with residues of ASP 64, VAL 65, GLY 96, GLY 14, SER 20,THR 196, ILE 194 and GLY 192. The water molecule formed hydrogen bond with phosphate OH of compound and SER 94.It had Pie-Pie stacking with PHE 41 and PHE149.
Conclusion
Most of the compounds exhibit hydrophobic interaction. The Pie- pie stacking interaction with PHE 41 and PHE 149. Isatin and Eugenol had interaction with the target as that of the standard isoniazid whereas the other compounds showed interaction like the validated compound. Then isatin and eugenol can be tested against mycobacterium tuberculi. This lead compound may lead to a novel class of anti-TB drugs in the future.