Nowadays, the patient safety is seriously jeopardized by the emergence and spread of nosocomial pathogens in
the form of biofilm that is resistant to traditional and affordable antimicrobials. Although advances in organic synthesis
have extended the lifetime of classic antibiotics through synthetic modifications, the search of innovative antibiofilm
compounds from natural sources can provide new templates, novel targets and unique mechanisms that should have advantages
over known antimicrobial agents. Testing sub-lethal concentrations of crude extracts and/or isolated compounds
from plants and microorganisms is critical to acting on mechanisms subtler than the killing activity, e.g. those influencing
the multicellular behavior, offering an elegant way to develop novel antimicrobial-free antibiofilm strategies.
Herein we discussed the search and biological activity of small molecules from natural sources and their synthetic derivatives
able to modulate biofilm genesis of nosocomial pathogens through non-microbicidal mechanisms (sub-lethal concentrations).
The present work offers an overview about the approaches applied to the discovery of lead small molecules including
a) conventional drug design methods like screening of chemical compounds obtained from nature and b) computer-
aided drug design approaches. Finally, a classification (not exhaustive but representative) based on the natural origin
of small molecules and their synthetic derivatives was reported.
The information presented in this review should be of interest to a broad range of disciplines and represents an effort to
summarize experimental research and advances in this field.