The most recent acquisitions on
chemotherapy and
chemoprophylaxis of
malaria are reviewed. With regard to
chemotherapy, candidate
antimalarial compounds have been divided into four groups, according to their stages of development.
Mefloquine and the combination of
mefloquine with
sulfadoxine/pyrimethamine belong to the first group: they have completed clinical trials and have been registered in several countries for routine clinical use. The second group is characterized by chemical compounds which are in an advanced stage of development, including clinical trials. The compounds considered in this group are: a) the 9-phenanthrenemethanols, among which
halofantrine is the most promising one; b) the
sesquiterpene lactones such as
Qinghaosu,
artemether,
artesunate,
artesunic acid and
arteether which must be further tested in order to find more effective
drug regimens capable of eliminating recrudescences and for the completion of toxicity studies; c)
pyronaridine, which appears to be a promising
antimalarial, effective also against
chloroquine-resistant P. falciparum, but still requiring further investigations on resistance and cross-resistance, as well as its pharmacokinetics, tolerability and bioavailability; d)
enpiroline, another promising compound, which needs to be further studied in Phase II and Phase III investigations with naturally acquired
malaria. The third group is composed of seven chemical classes of compounds that are in an advanced pre-clinical development, namely: the 4-
aminoquinolines, such as dabechin,
piperaquine,
hydroxypiperaquine,
tripiperaquine, dichlor-quinazine and the
Mannich base compounds, the 8-
aminoquinolines, the 4-quinolinemethanols, the
quinolones, the
naphthoquinones, the
quinazolines and the dihydrotriazines. Among the many
antimalarial compounds of interest, which can be considered at the moment as leads for further studies, only the acridandione derivatives such as
floxacrine, the
antibiotics, antifungal agents or their metabolites, plant substances such as
Yingzhaosu A and
quassinoids have been mentioned.
Malaria chemoprophylaxis, especially in
chloroquine-resistant P. falciparum areas, has become a real problem. The attempts to secure protection under these circumstances with the utilization of
amodiaquine, the combination of
sulfadoxine/pyrimethamine (
Fansidar),
sulfalene/
pyrimethamine (
Metakelfin), of
pyrimethamine/
dapsone (
Maloprim), with or without
chloroquine, had to be abandoned or to be used with caution in view of the severe complications following the weekly administration of these drugs. The combination of
chloroquine with
proguanil or
chlorproguanil, which could be recommended on theoretical bases, did not meet the expectations when tested in the field. (ABSTRACT TRUNCATED AT 400 WORDS)