biostudies-literatureSeo HKorea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of KoreaSoonchunhyang University Research Funde3001648https://www.ebi.ac.uk/biostudies/studies/S-EPMC9154192biostudies-literatureUnknown20(5)The continued spread of drug-resistant tuberculosis is one of the most pressing and complex challenges facing tuberculosis management worldwide. Therefore, developing a new class of drugs is necessary and urgently needed to cope with the increasing threat of drug-resistant tuberculosis. This study aims to discover a potential new class of tuberculosis drug candidates different from existing tuberculosis drugs. By screening a library of compounds, methyl (S)-1-((3-alkoxy-6,7-dimethoxyphenanthren-9-yl)methyl)-5-oxopyrrolidine-2-carboxylate (PP) derivatives with antitubercular activity were discovered. MIC ranges for PP1S, PP2S, and PP3S against clinically isolated drug-resistant Mycobacterium tuberculosis strains were 0.78 to 3.13, 0.19 to 1.56, and 0.78 to 6.25 μg/ml, respectively. PPs demoPLoS biologyA novel class of antimicrobial drugs selectively targets a Mycobacterium tuberculosis PE-PGRS protein.PMC9154192HI13C0828Kim SNam KWSong HYYoon YGil YSCho HDSeo HIslam MILee BEChoi JMahmud HAfalseA novel class of antimicrobial drugs selectively targets a Mycobacterium tuberculosis PE-PGRS protein.The continued spread of drug-resistant tuberculosis is one of the most pressing and complex challenges facing tuberculosis management worldwide. Therefore, developing a new class of drugs is necessary and urgently needed to cope with the increasing threat of drug-resistant tuberculosis. This study aims to discover a potential new class of tuberculosis drug candidates different from existing tuberculosis drugs. By screening a library of compounds, methyl (S)-1-((3-alkoxy-6,7-dimethoxyphenanthren-9-yl)methyl)-5-oxopyrrolidine-2-carboxylate (PP) derivatives with antitubercular activity were discovered. MIC ranges for PP1S, PP2S, and PP3S against clinically isolated drug-resistant Mycobacterium tuberculosis strains were 0.78 to 3.13, 0.19 to 1.56, and 0.78 to 6.25 μg/ml, respectively. PPs demo2022-01-01T00:00:00Z2022 May2025-04-22T11:51:54.117Z2025-04-06T00:08:22.492ZS-EPMC91541923563977310.1371/journal.pbio.3001648