InVitro Antimycobacterial Activities ofNewly Synthesized Benzoxazinorifamycins

strains), 100;andM. chelonae subsp. abscessus andM.chelonae subsp. chelonae, >100.Thesevalues aremore than64times lower thanthose ofRMP,except forthevalues against RMP-resistant M. tuberculosis (8timeslower) andthose against rapid growers,including M.fortuitum andM. chelonae (the same as thoseofRMP).Theother derivatives hadsimilar levels ofinvitroactivity against thesemycobacteria. When murineperitoneal macrophages inwhichM. intracellulare was phagocytosed invitro were cultured inthepresenceofthe benzoxazinorifamycins (1,ug/ml), muchmore rapid killing oftheorganisms ingested inthemacrophages was seencompared withwhenthesame amountofRMP was addedtothemedium.Theaddition ofbenzoxazinorifamycins attheconcentration of0.05,ig/ml caused more markedsuppression ofintracellular growth ofthe organismscompared withaddition ofRMP.KRM-1648andKRM-1657inhibited intracellular growth ofM. tuberculosis, andtheir efficacies were muchgreater thanthatofRMP.