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Antibiotics in development targeting protein synthesis
Author(s) -
Sutcliffe Joyce A.
Publication year - 2011
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2011.06323.x
Subject(s) - antibiotics , efflux , antimicrobial , multiple drug resistance , antibiotic resistance , microbiology and biotechnology , computational biology , biology , chemistry , biochemistry
The resolution of antibiotic–ribosomal subunit complexes and antibacterial–protein complexes at the atomic level has provided new insights into modifications of clinically relevant antimicrobials and provided new classes that target the protein cellular apparatus. New chemistry platforms that use fragment‐based drug design or allow novel modifications in known structural classes are being used to design new antibiotics that overcome known resistance mechanisms and extend spectrum and potency by circumventing ubiquitous efflux pumps. This review provides details on seven antibiotics in development for treatment of moderate‐to‐severe community‐acquired bacterial pneumonia and/or acute bacterial skin and skin structure infections: solithromycin, cethromycin, omadacycline, CEM‐102, GSK1322322, radezolid, and tedizolid. Two antibiotics of the oxazolidinone class, PF‐02341272 and AZD5847, are being developed as antituberculosis agents. Only three antibiotics that target the protein cellular machinery, TP‐434, GSK2251052, and plazomicin, have a spectrum that encompasses multidrug‐resistant Gram‐negative pathogens. These compounds provide hope for treating key pathogens that cause serious disease in both the community and the hospital.