Fragment Discovery for the Design of Nitrogen Heterocycles as Mycobacterium tuberculosis Dihydrofolate Reductase Inhibitors.
Fragment-based drug design was used to identify Mycobacterium tuberculosis (Mtb) dihydrofolate reductase (DHFR) inhibitors. Screening of ligands against the Mtb DHFR enzyme resulted in the identification of multiple fragment hits with IC50 values in the range of 38-90 μM versus Mtb DHFR and minimum inhibitory concentration (MIC) values in the range of 31.5-125 μg/mL. These fragment scaffolds would be useful for anti-tubercular drug design.
Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, India.
Rupesh U
RU
Shelke
Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, India.
Mariam S
MS
Degani
Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, India.
Archana
A
Raju
Radiation Medicine Centre, Tata Memorial Hospital, Parel, Mumbai, India.
Mukti Kanta
MK
Ray
Radiation Medicine Centre, Tata Memorial Hospital, Parel, Mumbai, India.
Mysore G R
MG
Rajan
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D009584:Nitrogen / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
D000995:Antitubercular Agents; D005493:Folic Acid Antagonists; D006571:Heterocyclic Compounds; D013762:Tetrahydrofolate Dehydrogenase; D009584:Nitrogen
DHFR; FBDD; Mycobacterium tuberculosis; Nitrogen heterocycles