The 4-quinolone-3-carboxylic acid motif as a multivalent scaffold in medicinal chemistry.
Quinolones are among the most common frameworks present in the bioactive molecules and hence represent an attractive starting point for the design of combinatorial libraries. Since 1962 4-quinolone-3-carboxylic acid derivatives are clinically used as antibacterial agents worldwide. Currently, fluoroquinolones are approved by the WHO as second-line drugs to treat tuberculosis (TB), and their use in multidrug-resistant (MDR)-TB is increasing due to the fact that they have a broad and potent spectrum of activity and can be administered orally. In the last years, quinolones endowed with "non-classical" biological activities, such as antitumor, anti-HIV-1 integrase, cannabinoid receptor 2 agonist/antagonist activities, have been reported by our research group as well as by other researchers. This review focuses on the 4-quinolone-3-carboxylic acid motif as a privileged structure in medicinal chemistry for obtaining new compounds possessing antibacterial, antitumor, anti-HIV, and cannabinoid receptors modulating activities. Synthetic approaches, structure-activity relationships, mechanisms of action, and therapeutic potentials of these novel classes of pharmacologically active compounds are presented.
Dipartimento Farmaco Chimico Tecnologico, Universitá degli Studi di Siena Via A. Moro, snc 53100 Siena, Italy.
Claudia
C
Mugnaini
Serena
S
Pasquini
Federico
F
Corelli
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry*; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000737:chemistry*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D019428:HIV Integrase Inhibitors; D015363:Quinolones; D043885:Receptor, Cannabinoid, CB2