From: Natural products as starting points for future anti-malarial therapies: going back to our roots?
Mechanism of action
Highest level demonstration of activity
Assumed to be similar to chloroquine – and prevent heme polymerisation.
Early reports of activity with Cinchona bark showed partial activity with 60g bark over up to 21 days. This represents a total dose of 350 -700 mg, compared to a current clinical dose of 500 mg (10 mg/kg salt) given three times a day for seven days currently - suggesting the bark treatment was unlikely to be completely effective 
Lapachol Lapinone Atovaquone
Electron transport inhibition
Lapachol is a naphthoquinone used to treat malaria and fevers  reported in the 19th century; it showed weak activity against P. zophurae infected ducks, when tested in 1943. Lapinone (a close derivative) was confirmed active in patients with P vivaxby intravenous administration for four days (N=9). Chemical optimisation of the scaffold led to atovaquone
Free radical activation in the presence of free ferrous iron – liberated in erythrocytes by parasite digestion of haemaglobin
Traditional Chinese Medicine. Tea made from 5 g/l leaves gave 12 mg artemisinin, and clears parasite in 3-4 days . (Partial protection, since this is much lower than the WHO recommended dose). More recent studies  achieved doses of 95 mg, with 70% cure on day 7, but still with high recrudesence and only 30% cure at day 28 . Chemical optimization has led to longer acting synthetic endoperoxides, currently in development.
Artabotrys uncinatus (Ying Zhao)
Presumed to be free radical activation in the presence of free ferrous iron – liberated in erythrocytes by parasite digestion of haemoglobin.
Traditional Chinese medicine. The active ingredient was modified to make Ro-41-3823 which was: Single tested in patients (N=30) aged 12 -42 years, with parasitaemia > 5000/ml and temperature 37.7 -39.8 oC. 80% patients were parasite free at day 7 with a single dose of 25 mg/kg. Discontinued because of lack of superiority over mefloquine or artemisinin, and because of safety concerns.
DNA intercalation 
Patients between 16 and 60, (N=12) with parasitaemia between 1000 and 10000/ul given 25 mg/kg extract tid for seven days. No recrudescence at day 28. Cryptolepine administered orally to P. berghei-infected mice in doses of 50mg/kg/day for four days reduced parasitaemia by 80% but the mice were not cured of malaria (Wright et al., 1996) . Decoction has been standardized by the Faculty of Pharmacy, Kwame Nkrumah University of Science and Technology, Ghana and is marketed as PHYTO-LARIA®.
45 patients have been treated with a nanomilled curcumin, both vivax and falciparum malaria. Nanomilling is used to improves bioavailability. No clinical data on parasitaemia or fever available S Kumesh Kar pers. comm
Traditional treatment from DR Congo, Herbal medicinal Product PR 259 CT1 – completed a phase I trial – 1000 mg t.i.d for 7 days  Phase IIb (N=65 patients) treated with 1000 mg tid for three days, followed by 500 mg tid per day for four days. Parasitaemia fulfilled the WHO research criteria for malaria. ACPR at day 14 was 90.3% compared with ASAQ at 96.9%.. Shown to be orally active in murine models but not in vitro suggesting that deglycosylation may be required for activity.
Protopine Allocryptopine Berberine
Initial study (N=80) with 80% patients < 5 years old. Showed need for high dose regimen . Follow up study (N=199) vs amodiaquine artesunate (N=102)  median age 5 years given for 7-14 days twice per day 89% successful at day 28, compared with a 95% success rate for ASAQ. P atients had low parasitaemia (<1000/μL), with only 17.8% of patients fulfilled the WHO research criteria for clinical malaria.
Known as omubirizi in southwestern Uganda and used for pain relief and malaria attack, obtained from The Medical Traditional Healer Association in Rukararwe, Bushenyi District, Uganda  Clinical study for decoction (N=33) infusion given four times per day for 7 days  67% response, inclusion criteria allowed patients with <2000/uL and temperature <37.5 oC. All patients over 12 years old
Ch’ang shan, is a traditional Chinese anti-malarial herb. Reports from 1942 suggest a dose of 60 mg was clinically effective . Adverse reaction prevented widespread use of febrifugine. Halofuginone, a halogenated derivative is used against coccidiosis, and other derivatives have been tested against Plasmodium 
HSP90 inhibitor ?
Neem extracts are known to be active based on traditional and observations from India in the early 20th century . No published recent clinical studies on malaria, although the aqueous/acetone extract is safe  and is registered in Nigeria in 250mg capsules as IRACARP®, adult treatment costs of around $6.00. Most potent ingredient is gedunin . Murine activity is variable and requires cytochrome 3A4 inhibitor.