title: Anti-tubercular agents from Glycyrrhiza glabra.
abstract: Bioactivity guided isolation of Glycyrrhiza glabra (Leguminosae / Fabaceae) roots resulted in the characterization of 18β-glycyrrhetinic acid as a major anti-tubercular agent. Further, GA-1 was semi-synthetically converted into its nine derivatives, which were in-vitro evaluated for their antitubercular potential against Mycobacterium tuberculosis H37Rv using BACTEC-460 radiometric susceptibility assay. All the derivatives were active, but the benzylamide (GA-8, MIC 12.5μg/ml) and ethyl oxylate (GA-3, MIC 25.0 μg/ml) derivatives were significantly active against the pathogen. This was further supported by the molecular docking studies, which showed adequate docking (LibDock) scores for GA-3 (120.3) and GA-8 (112.6) with respect to the standard anti-tubercular drug, rifampicin (92.94) on the DNA-directed RNA polymerase subunit beta (rpoB) target site. Finally, the in silico pharmacokinetic and drug-likeness studies showed that GA-3 and GA- 8 possesses drug-like properties. This is the first ever report on the anti-tubercular potential of GA and its derivatives. These results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non toxic natural product.
authors: Komal
authors: K
authors: Kalani
authors: Vinita
authors: V
authors: Chaturvedi
authors: Sarfaraz
authors: S
authors: Alam
authors: Feroz
authors: F
authors: Khan
authors: Medicinal Chemistry Department, CSIR-CIMAP, Lucknow-226015, India. santoshkumar_1955@yahoo.com.
authors: Santosh Kumar
authors: SK
authors: Srivastava
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D012321:DNA-Directed RNA Polymerases; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D018517:Plant Roots / Q000737:chemistry; D011487:Protein Conformation; D051381:Rats; D018675:Toxicity Tests / Q000379:methods
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; C119129:18alpha-glycyrrhetinic acid; D012321:DNA-Directed RNA Polymerases; D006034:Glycyrrhetinic Acid