J Chem Inf Model - Identification of a new class of FtsZ inhibitors by structure-based design and in vitro screening.

Tópicos

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Resumo

The Filamenting temperature-sensitive mutant Z (FtsZ), an essential GTPase in bacterial cell division, is highly conserved among Gram-positive and Gram-negative bacteria and thus considered an attractive target to treat antibiotic-resistant bacterial infections. In this study, a new class of FtsZ inhibitors bearing the pyrimidine-quinuclidine scaffold was identified from structure-based virtual screening of natural product libraries. Iterative rounds of in silico studies and biological evaluation established the preliminary structure-activity relationships of the new compounds. Potent FtsZ inhibitors with low micromolar IC50 and antibacterial activity against S. aureus and E. coli were found. These findings support the use of virtual screening and structure-based design for the rational development of new antibacterial agents with innovative mechanisms of action.

Resumo Limpo

filament temperaturesensit mutant z ftsz essenti gtpase bacteri cell divis high conserv among gramposit gramneg bacteria thus consid attract target treat antibioticresist bacteri infect studi new class ftsz inhibitor bear pyrimidinequinuclidin scaffold identifi structurebas virtual screen natur product librari iter round silico studi biolog evalu establish preliminari structureact relationship new compound potent ftsz inhibitor low micromolar ic antibacteri activ s aureus e coli found find support use virtual screen structurebas design ration develop new antibacteri agent innov mechan action

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