Epigallocatechin Gallate, a Green Tea Polyphenol Inhibits Mycobacterium smegmatis: In silico and In vitro Studies

Abstract

Narayanan and Ramesh: Epigallocatechin Gallate Inhibits M. smegmatisPresence of multidrug resistant strains makes treatment of tuberculosis difficult. Conventional frontline antituberculosis therapy has high incidence of treatment failure due to non-adherence and severe side effects, and therefore warrants alternative approaches using safe, natural compounds. (-) Epigallocatechin gallate, a green tea catechin with significant antimicrobial properties, and its derivatives have been studied for their inhibitory effects on Mycobacterium smegmatis. Enoyl reductase (Inh A, PDB ID: 2NV6), an important drug target inhibited by the antituberculosis drug, isoniazid, was docked with geometrically optimized conformation of epigallocatechin gallate and two of its derivatives using AutoDock software. Perpropionate and permethyl derivatives of epigallocatechin gallate were synthesized and, along with epigallocatechin gallate, evaluated for their inhibitory and cytotoxic properties against M. smegmatis using microplate dilution method and alamarBlue® assay, respectively. Ames test was performed to assess the mutagenic potential of epigallocatechin gallate. It was docked successfully onto the InhA with docking energy of -9.38 kcal mol -1 . Analysis of neighbouring groups revealed 11 amino acid residues common to both isoniazid and epigallocatechin gallate. The minimum inhibitory concentrations for epigallocatechin gallate, perpropionate and permethyl were found to be 128 (58.2% inhibition), 8 (32.9%) and 4 (12.5%) µg/ml, respectively. Epigallocatechin gallate showed a cytotoxicity of 18.6% at a concentration of 8 µg/ml, while the two derivatives did not show any toxicity, even at 64 µg/ml. Ames test revealed the absence of mutagenicity for epigallocatechin gallate, in presence and absence of metabolic activation. Nonmutagenic epigallocatechin gallate inhibits the growth of M. smegmatis and warrants further investigation as an adjunct therapy for pathogenic mycobacteria.

(−)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer

“…Aiming to understand this differential affinity, a future perspective of our group will be to gain insights, through molecular docking analyses, in the potential binding modes of G28 and monoesters to their target FASN catalytic domains. These domains are probably the same as those targeted by EGCG, the NADPH-dependent domains ketoreductase (KR) [ 35 ] and enoyl reductase (ER) [ 36 , 37 , 38 , 39 ], which participate in the saturation of the growing fatty acid chain [ 40 ]. Interestingly, EGCG has been shown to compete with NADPH/NADH for binding to KR and ER [ 35 , 36 , 37 , 38 , 39 ].…”

“…These domains are probably the same as those targeted by EGCG, the NADPH-dependent domains ketoreductase (KR) [ 35 ] and enoyl reductase (ER) [ 36 , 37 , 38 , 39 ], which participate in the saturation of the growing fatty acid chain [ 40 ]. Interestingly, EGCG has been shown to compete with NADPH/NADH for binding to KR and ER [ 35 , 36 , 37 , 38 , 39 ]. Since both NADPH/NADH (FASN) and GTP (FtsZ) are nucleotides, it is worth noting that, in the FtsZ study, the galloyl groups and the naphthalene scaffold of G28 were predicted to replace the interactions by the phosphates and the nucleobase of the nucleotide, respectively [ 26 ].…”

Polyphenols as Therapeutics in Respiratory Diseases: Moving from Preclinical Evidence to Potential Clinical Applications

“…Epigallocatechin gallate showed a cytotoxicity of 18.6% at eight µg/ml, while the two derivatives did not show any toxicity. The non-mutagenic epigallocatechin gallate inhibits M. smegmatis growth and warrants further investigation as an adjunct therapy for pathogenic mycobacteria 86 .…”

Naturally Occurring Green Tea Polyphenols as Anti-Mycobacterial Agents

“…In a very recent study, GTP epigallocatechin-3-gallate was demonstrated to inhibit InhA, the enoyl-ACP reductase of mycobacterium. This has prompted us to screen in silico a set of GTPs against various pivotal targets of mycobacterium including InhA [6,7]. For the best-docked top three hits with higher docking scores, we listed down their drug-likeness assessment, and ADMET (absorption, distribution, metabolism, excretion, toxicity) properties.…”