Inhibition of Bacterial RNase P RNA by Phenothiazine Derivatives.
There is a need to identify novel scaffolds and targets to develop new antibiotics. Methylene blue is a phenothiazine derivative, and it has been shown to possess anti-malarial and anti-trypanosomal activities. Here, we show that different phenothiazine derivatives and pyronine G inhibited the activities of three structurally different bacterial RNase P RNAs (RPRs), including that from Mycobacterium tuberculosis, with Ki values in the lower μM range. Interestingly, three antipsychotic phenothiazines (chlorpromazine, thioridazine, and trifluoperazine), which are known to have antibacterial activities, also inhibited the activity of bacterial RPRs, albeit with higher Ki values than methylene blue. Phenothiazines also affected lead(II)-induced cleavage of bacterial RPR and inhibited yeast tRNA(Phe), indicating binding of these drugs to functionally important regions. Collectively, our findings provide the first experimental data showing that long, noncoding RNAs could be targeted by different phenothiazine derivatives.
Department of Cell and Molecular Biology, Box 596, Biomedical Centre, Uppsala SE-751 24, Sweden. littleyaya830@icloud.com.
Shiying
S
Wu
Department of Cell and Molecular Biology, Box 596, Biomedical Centre, Uppsala SE-751 24, Sweden. guanzhong.mao@icm.uu.se.
Guanzhong
G
Mao
Department of Cell and Molecular Biology, Box 596, Biomedical Centre, Uppsala SE-751 24, Sweden. Leif.Kirsebom@icm.uu.se.
Leif A
LA
Kirsebom
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D007854:Lead / Q000494:pharmacology; D010640:Phenothiazines / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000378:metabolism; D012331:RNA, Fungal / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D043262:Ribonuclease P / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D014150:Antipsychotic Agents; D001426:Bacterial Proteins; D010640:Phenothiazines; D012329:RNA, Bacterial; D012331:RNA, Fungal; D007854:Lead; D012343:RNA, Transfer; D043262:Ribonuclease P
RNA processing; RNase P; catalytic RNA; phenothiazines