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novel terminal bipheny-based diapophytoene desaturases (crtn) inhibitors as anti-mrsa/visr/lrsa agents with reduced herg activity
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نویسنده
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li b. ,ni s. ,mao f. ,chen f. ,liu y. ,wei h. ,chen w. ,zhu j. ,lan l. ,li j.
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منبع
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journal of medicinal chemistry - 2018 - دوره : 61 - شماره : 1 - صفحه:224 -250
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چکیده
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Crtn has been identified as an attractive and druggable target for treating pigmented staphylococcus aureus infections. more than 100 new compounds were synthesized, which target the overwhelming the defects of the crtn inhibitor 1. analogues 23a and 23b demonstrated a significant activity against pigmented s. aureus newman and 13 mrsa strains (ic 50 = 0.02-10.5 nm), along with lower herg inhibition (ic 50 > 30 μm, ∼10-fold decrease in comparison with 1). furthermore, 23a and 23b were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. remarkably, 23a could strongly block the pigment biosynthesis of these nine multidrug-resistant mrsa strains, including excellent activity against lrsa strains and visa strains in vivo, and all of which demonstrated that 23a has a huge potential against intractable mrsa, visa, and lrsa issues as a therapeutic drug.
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آدرس
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east china university of science and technology, school of pharmacy, shanghai key laboratory of new drug design, china, east china university of science and technology, school of pharmacy, shanghai key laboratory of new drug design, china, east china university of science and technology, school of pharmacy, shanghai key laboratory of new drug design, china, chinese academy of sciences, shanghai institute of materia medica, state key laboratory of drug research, china, east china university of science and technology, school of pharmacy, shanghai key laboratory of new drug design, china, east china university of science and technology, school of pharmacy, shanghai key laboratory of new drug design, china, east china university of science and technology, school of pharmacy, shanghai key laboratory of new drug design, china, east china university of science and technology, school of pharmacy, shanghai key laboratory of new drug design, china, chinese academy of sciences, shanghai institute of materia medica, state key laboratory of drug research, china, east china university of science and technology, school of pharmacy, shanghai key laboratory of new drug design, china
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Authors
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