Quinoline scaffold as a privileged substructure in antimicrobial drugs

Drug design is a complex issue that still lack general approach with proven reliability. Combinatorial chemistry and HTS techniques did not appear to be effort-effective. As an alternative we have the fragment based design and more recently so called the privileged structures approach. We believe that some structural subunits are especially effective in design of bioeffectors. However it is not clear what makes one molecular scaffold more privileged than another. Overall frequency of appearance of molecular scaffold in bioactive compounds or natural substances may be used as a good factor of qualitative discriminator of privileged structures. According this, the quinoline scaffold, due to its frequent appearance in bioactive substances can be regarded as a privileged structure. It is abundant in number of natural compounds such as alkaloids: quinine, camptothecin or cinchonidine. In synthetic medicinal chemistry the quinoline motif is widely exploited revealing a spectrum of activity covering anticancer, antifungal, antibacterial and antiprotozoic effects. In fact, introducing chloroquine into treatment of malaria more than 60 years ago triggered a new era of quickly developing antimicrobial drugs through nalidixic acid and fluoroquinolones. In this review we wish to explore antimicrobial quinolines as an important class of drugs from both natural and synthetic sources.