The synthesis and biological activity of nitrogen containing chalcones and analogues

Malaria is a global health problem, with an estimated 300–500 million new clinical cases and 1–2 million fatalities reported annually. Almost 90% of the incidences of malaria and deaths from the disease occur in sub-Saharan Africa. Since malaria affects mainly the poor, it is not profitable for pharmaceutical companies to develop new treatments; thus malaria is classified as a „neglected‟ or „orphan disease‟. Malaria in humans, transmitted by female Anopheles mosquitoes, is caused by four species of Plasmodium, of which P. vivax is the most common malaria parasite, while the most severe form of malaria is caused by P. falciparum. These protists, the targets of antimalarial drugs, gradually develop resistance to malarial drugs. For example, quinine from the bark of the cinchona tree was the first drug against malaria. When it became obsolete in the 1940s it was replaced by chloroquine (CQ), a synthetic analogue, which is also reaching a stage of obsolescence. Many of the subsequently developed drugs are structurally related to chloroquine; thus they are or will soon be ineffective. Artemisinin, developed from an ancient Chinese herbal medication for fever, is the latest antimalarial drug of choice. It is structurally unrelated to aminoquinoline, but resistance has already been observed in East Asia. Derivatives – including artesunate, dihydroartemisinin, artemether and arteether – are often used in combination with other antimalarial compounds to increase the half-life of a drug and delay the development of resistance to it. Because flavonoids are not detected in human blood after oral administration (i.e. are not bioavailable), it is difficult to explain the plethora of biological activities and beneficial dietary effects reported for flavonoids. The low bioavailability of polyphenols is explained by their poor absorption in the intestines and their rapid enzymatic degradation in blood. Furthermore, according to the Lipinski rules, most commercially available drugs