Docking- and pharmacophore-based virtual screening for the identification of novel Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) inhibitor with a thiobarbiturate scaffold

• Published in: Bioorganic chemistry Vol. 85; pp. 229 - 239
• Main Authors: Zhang, Dongfeng, Lin, Yun, Chen, Xi, Zhao, Wenting, Chen, Dongni, Gao, Meng, Wang, Qinglin, Wang, Bin, Huang, Haihong, Lu, Yongjun, Lu, Yu
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.04.2019; Elsevier
• Subjects: Animals; Antitubercular Agents - chemical synthesis; Antitubercular Agents - metabolism; Antitubercular Agents - pharmacology; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Biochemistry & Molecular Biology; Catalytic Domain; Cell Line; Chemistry; Chemistry, Organic; Docking; Drug Evaluation, Preclinical; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Humans; Life Sciences & Biomedicine; Mice; Microsomes, Liver - metabolism; Molecular Docking Simulation; Molecular Structure; MptpB inhibitor; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - enzymology; Pharmacophore; Physical Sciences; Protein Binding; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases - metabolism; Science & Technology; Structure-Activity Relationship; Thiobarbiturate scaffold; Thiobarbiturates - chemical synthesis; Thiobarbiturates - metabolism; Thiobarbiturates - pharmacology; Tuberculosis; Virtual screening; Virtual screening; Docking; Thiobarbiturate scaffold; Tuberculosis; MptpB inhibitor; Pharmacophore; POTENT; DRUG DISCOVERY; STRATEGIES

[Display omitted] •A novel MptpB inhibitor was identified by performing virtual screening strategy.•Compound 15 exhibited good druggability profiles.•Compound 15 exhibited potent inhibition of intracellular Mtb growth in macrophage.•Compound 15 was an excellent lead for further elaborations to devel...