Antifolate Activity of Plant Polyphenols against Mycobacterium tuberculosis.
With the view of exploring phytochemicals as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors, known plant polyphenols from various classes were subjected to detailed docking studies. From this in-silico screening, seven polyphenols were selected and tested against Mtb H37 Rv in whole cell assays. The phytochemicals exhibited potential activity ranging from 3 to 183 µm. These molecules were then tested against the pathogenic and human enzymes in a high-throughput microtitre assay. Epigallocatechin gallate showed the best activity and selectivity. The in-silico analysis was in agreement with the assay results. Of these 7 polyphenols, 5 exhibiting minimum inhibitory concentration values of ≤15 µm were tested for synergistic activity with first line drug Ethambutol and second line folate inhibitor para-amino salicylic acid. Epigallocatechin gallate, Magnolol and Bakuchiol exhibited moderate synergistic association by lowering the minimum inhibitory concentration of these drugs. These simple phytochemicals could hence be considered as leads for further studies, or for preparation of semi-synthetic derivatives to be used in combination therapy, for increased anti-tuberculosis activity after validation in-vivo.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, Maharashtra, 400019, India.
Archana
A
Raju
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, Maharashtra, 400019, India.
Mariam S
MS
Degani
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, Maharashtra, 400019, India.
Mihir P
MP
Khambete
Tuberculosis Immunology and Immunoassay Development Section, Radiation Medicine Centre-BARC, Tata Memorial Hospital- Annexe Bldg, Parel, Mumbai, Maharashtra, 400012, India.
M K
MK
Ray
Tuberculosis Immunology and Immunoassay Development Section, Radiation Medicine Centre-BARC, Tata Memorial Hospital- Annexe Bldg, Parel, Mumbai, Maharashtra, 400012, India.
M G R
MG
Rajan
D002392:Catechin / Q000031:analogs & derivatives; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D064209:Phytochemicals; D059808:Polyphenols
D005493:Folic Acid Antagonists; D064209:Phytochemicals; D059808:Polyphenols; D002392:Catechin; C045651:epigallocatechin gallate
dihydrofolate reductase; in-silico studies; plant polyphenols; synergy; tuberculosis