The antibiotics in the chemical space.
Ensuring the availability of new antibiotics to eradicate resistant pathogens is a critical issue, but very few new antibacterials have been recently commercialized. In an effort to rationalize their discovery process, the industry has utilized chemical library and high-throughput approaches already applied in other therapeutical areas to generate new antibiotics. This strategy has turned out to be poorly adapted to the reality of antibacterial discovery. Commercial chemical libraries contain molecules with specific molecular properties, and unfortunately systemic antibacterials are more hydrophilic and have more complex structures. These factors are critical, since hydrophobic antibiotics are generally inactive in the presence of serum. Here, we review how the skewed distribution of systemic antibiotics in chemical space influences the discovery process.
Gualtieri
Maxime
M
Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Montpellier, France.
Banéres-Roquet
Françoise
F
Villain-Guillot
Philippe
P
Pugnière
Martine
M
Leonetti
Jean-Paul
JP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001688:Biological Products; D012709:Serum Albumin