title: The antibiotics in the chemical space.
abstract: 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.
authors.affiliation: Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Montpellier, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Gualtieri
authors.forename: Françoise
authors.initials: F
authors.lastname: Banéres-Roquet
authors.forename: Philippe
authors.initials: P
authors.lastname: Villain-Guillot
authors.forename: Martine
authors.initials: M
authors.lastname: Pugnière
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Leonetti
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D012709:Serum Albumin