Progress in the Development of Anti-malarial Quinolones
Progress in the Development of Anti-malarial Quinolones
Quinolones are synthetic compounds containing the 4-oxo-1,4-dihydroquinoline skeleton that may be written as the tautomeric 4-hydroxyquinoline (Figure 3). They are mostly used as antibiotics. The first anti-bacterial quinolone, nalidixic acid, was discovered as a by-product during the synthesis of CQ. Since the discovery of nalidixic acid and its anti-bacterial properties against gram negative bacteria, several structural modifications have been made to widen its spectrum of activity to also include gram positive bacteria.
(Enlarge Image)
Figure 3.
The quinolone scaffold.
Besides possessing bactericidal properties, the quinolone scaffold is present in the structures of certain anti-cancer and anti-viral drugs, and also in anti-oxidants. The scaffold is also incorporated into compounds that display anti-malarial activity.
Reports on the anti-malarial properties of quinolones, compared to their anti-bacterial properties, are relatively limited. Recent research involving the evaluation of anti-malarial properties of quinolones, however, indicates that these compounds demonstrate promising potential. They show very good efficacies and target more than one stage of the malaria parasite life cycle, including the blood, liver and gametocyte stages. They also seem to have novel modes of action, different from those of most of the current, clinically used drugs. Thus, in this review are presented details of anti-malarial quinolones documented within the past six years.
The Quinolone Scaffold
Quinolones are synthetic compounds containing the 4-oxo-1,4-dihydroquinoline skeleton that may be written as the tautomeric 4-hydroxyquinoline (Figure 3). They are mostly used as antibiotics. The first anti-bacterial quinolone, nalidixic acid, was discovered as a by-product during the synthesis of CQ. Since the discovery of nalidixic acid and its anti-bacterial properties against gram negative bacteria, several structural modifications have been made to widen its spectrum of activity to also include gram positive bacteria.
(Enlarge Image)
Figure 3.
The quinolone scaffold.
Besides possessing bactericidal properties, the quinolone scaffold is present in the structures of certain anti-cancer and anti-viral drugs, and also in anti-oxidants. The scaffold is also incorporated into compounds that display anti-malarial activity.
Reports on the anti-malarial properties of quinolones, compared to their anti-bacterial properties, are relatively limited. Recent research involving the evaluation of anti-malarial properties of quinolones, however, indicates that these compounds demonstrate promising potential. They show very good efficacies and target more than one stage of the malaria parasite life cycle, including the blood, liver and gametocyte stages. They also seem to have novel modes of action, different from those of most of the current, clinically used drugs. Thus, in this review are presented details of anti-malarial quinolones documented within the past six years.
