OA11491A - Voacamine as anti-malarial agent and anti-malarialagent containing voacamine. - Google Patents
Voacamine as anti-malarial agent and anti-malarialagent containing voacamine. Download PDFInfo
- Publication number
- OA11491A OA11491A OA1200000261A OA1200000261A OA11491A OA 11491 A OA11491 A OA 11491A OA 1200000261 A OA1200000261 A OA 1200000261A OA 1200000261 A OA1200000261 A OA 1200000261A OA 11491 A OA11491 A OA 11491A
- Authority
- OA
- OAPI
- Prior art keywords
- voacamine
- extract
- strains
- malarial
- agent according
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Extraction Or Liquid Replacement (AREA)
- Compounds Of Unknown Constitution (AREA)
Abstract
The invention concerns voacamine as anti-malarial agent active against Plasmodium falciparum strains, including the resistant strains, as well as an anti-malarial agent containing as main active principle voacamine. A basic Pescheria extract, in particular Pescheria Fuchsiaefolia, can be used as anti-malarial agent having in particular voacamine as active principle.
Description
1 011491
VOACAMINE AS AN ANTI-MALARIAL AGENT ANDAN ANTI-MALARIAL AGENT CONTAINING VOACAMINE
The présent invention relates to voacamine and its use as an anti-malarial 5 agent having a powerful activity against ail Plasmodium strains being résistant or not.By résistant strains, we are talking about strains being résistant to quinolitic alkaloidssuch as quinine and chloroquine, as well as strains being résistant toaminocrinodines. 10 Voacamine or 12-methoxy-13-[(3a)-17-methoxy-17-oxovobasan-3-yl] ibogamine-18-carboxylate methyl, C^Hsz^Os, where the developed formula is givenbelow, is an bis-indolic alkaloid dimer that is found in numerous plant species thatbelongs to the genus Voacanga ( see US 2,823,204).
This alkaloid is known for its cytotoxic activity (J. Nat. Prod., 1994;, 57, 1517)25 and for its anti-bacterial activity against Gram positive bacteria as well as against
Gram négative bacteria (Phytochemistry, 1984, 23,1771).
The object of the présent invention is the use of voacamine as an anti-malarialagent, against ail Plasmodium strains, and more specifically against Plasmodium 30 falciparum including the résistant strains.
Paludism or malaria is a serious endemic disease which affects thepopulations of tropical and subtropical régions and is a carried by mosquitoes. Theparasite is a heamatozoa of the Plasmodium genus, for example Plasmodium vivax, 011491 2
Plasmodium ovale, Plasmodium malariae and particularly, the most dangerous,Plasmodium falciparum. This disease is fought by several drugs which are generallyquinolitic alkaloids, like chloroquine or aminocrinodines. Unfortunately, thePlasmodium hâve slowly developed résistance against these, particularly against 5 chloroquine, and this drug has become useless in numerous régions of the worldThere must be a substitution to other drugs such as aminocrinodines, which areunfortunately toxic.
According to the invention, the inventors hâve underscored the efficiency of 10 voacamine against Plasmodium strains including those who hâve become résistantto quinolitic alkaloids and to aminocrinodines, and this without any side effects knownto this day. The invention concerns, as a primary aspect, the use of voacamine asan anti-malarial agent 15 In another aspect, the invention concerns anti-malarial agents containing voacamine, in particular plant extracts that contain this alkaloid. The invention relatesto the basic extracts of plants of the Voacanga genus, but also to the basic extractsof other voacamine containing plants, in particular basic extracts from plants of thePeschiera genus (or Tabernaemontana), in particular Peschiera van heurckii, 20 Peschiera campestris, Peschiera affinis, Peschiera laeta and more particularlyPeschiera Fuchsiaefolia.
Peschiera Fuchsiaefolia, an apocyancea from the sub family ofTabernaemotanoideae, is an indigenous plant of South America, in particular the 25 Amazonian basin. Called « leitiero de vaca » in Brazil, it is a weed that infestspastures, and it is treated with pesticides. It has been recently reported that extracLfrom this plant can be used to neutralize cobra venom (J. Venemous Anima Toxins,1997, 3, 22). 30 The invention also concerns a basic extract of Peschiera, more precisely
Peschiera Fucsiaefolia, and more particularly a basic extract from the grains, the barkof the stems or the roots of the Peschiera Fuchsiaefolia, which is rich in tertiaryalkaloids. 011491 3
We hâve noticed, with no known explanations to this day, that the basicextract consisting in the fraction rich in tertiary alkaloids from the roots of the bark ofthe Péschiera Fuchsiaefolia had a superior activity to voacamine alone, probably bya synergistic effect with one of the other alkaloids présent in that extract, notably 5 perivine, 16-epi-affinise, affisine, voacamidine, 16’-decarbomethoxyvoacamine, Nb-demethylvoacamine, tabernamine, ervahanine A, vobasine, voachalotine, heynanine,voacristine, conopharyngine, coronaridine and voacangine having respectivelyformulas II, III and IV, given on the next page. 10 Tabernamine, ervahanine A, vobasine, conopharygine, heynanine, voacristine, coronaridine were isolated for the first time from this plant.
The other alkaloids are known and their formulas are given in The MerckIndex, page 9944. 15
With the help of voacamine or the basic plant extract that contains voacamine,it is possible to préparé médicaments in which one or many of the alkaloids présent,in the form of a free base or physiologically acceptable salts, are incorporated in apharmacologically acceptable support or excipient. 20
Another aspect of the invention concerne the process of isolation fromPeschiera, in particular Peschiera Fuchsiaefolia, of a basic extract that has someanti-malarial activities, as well as a process of isolation of voacamine from the same. 25 The extract in question can be prepared by treatment with a diluted acid of a dry ground material of Peschiera Fuchsiaefolia or a part of the plant only (root bark,stem bark) to extract the basic principles, followed by an alcalinization of the aqueousextract obtained at pH 9 and the extraction of the portion rich in tertiary alkaloid withan organic solvent, for example, dichloromethane. 30
The isolation of voacamine from this fraction rich in tertiary alkaloids isachieved by counter-current distribution between an aqueous phase and an organicphase by varying the pH of the aqueous phase. 011491 4 ίο 15 20
Périvine ie*épiaffinine ^2θΚϊ!ίΝ2^2
Vobasîne C21H24N2O3
Afflsine
CgoH^NzO
Voacalotine C21H23N2O3
H CHa
Hz
H
Ra COOCH3
CH2OH H
m
Ri Rz
IV 25 Cûronaridine H C20H25N2O2 Voacangine OMe C^gHgBNgOg Conopharyngine OMe 30 CjaHæNjOi Heynéanine H Voacristine OMe (Voacangérine)
H
H OMe
H
H
H
K
OH
OH 5 01149d
Voacamine, as well as the basic extracts containing it, notably the extracts ofPeschiera Fuchsiaefolia, can be prepared as médicament according to the classicalgalenical techniques, for example as injections, syrups, suppositories, tablets orcaplets, effervescent or not, or capsules. Of course, we will use pharmacologicallyacceptable excipients and supports such as sugar, lactose, etc.
In those pharmaceutical formulations, voacamine and the alkaloids whicheventually accompany it, can be found as free bases or physiologically acceptablesalts, like chlorohydrates, etc.
The invention will be better understood with référencé to the followingexamples, which are there purely to illustrate and not to limit. EXAMPLE 1
The starting material is the bark of the root of the Peschiera Fuchsiaefoliaharvested in Brazil, at Porto Alegre, which has been identified locally on a botanicalaspect, by the pharmaceutical industry Cibecol.
We treat 630 g of the finely pulverized végétal material by extraction (3 timéssuccessively) with 2 % aqueous acetic acid, we gather the eluted fraction, that wealcalinize at pH 9 with sodium carbonate, then we extract three times the aqueousalkaline phase with dichloromethane.
After combining the organic phases and eliminating the dichloromethane, weobtain a residue (12,1 g) that contains the tertiary alkaloids, that is the desired basicextract.
We measure in vitro the activity of this basic extract against Plasmodiumfalciparum strains, being résistant to chloroquine (W2) or being sensitive t.:chloroquine (D6). The activity is evaluated by evaluating IC50 (inhibitorconcentration). The résulte are given in Table 1 placed after Example 3. 011491 6 EXAMPLE 2
We separate the diverse tertiary alkaloids contained in the basic extract ofEXAMPLE 1 by counter-current distribution with dichloromethane as stationary phase 5 and an aqueous buffer with a pH decreasing by levels (mobile phase). The alkaloidsare recuperated from the aqueous phase by extraction with dichloromethane.
The equipment used is a Craig type Post apparatus made up of 200 glasstubes (with 10ml volumes for the lower phase and 10ml volumes for the upper 10 phase).
At pH 7, we obtain a first sériés of minor alkaloids, then at pH 5,2, are eluted irorder, perivine (Krx Kb = 4.10'9), 16-epi-affinine (Krx Kb= 2,5.10‘9), then affinisine(Krx Kt>= 7.1Ο'10). At pH 4, are eluted N-demethylvoacamine (Krx Kb= 3-5.10'11) and 15 vobasine (KrxKb=4.10‘11). At pH 3,2, are eluted voachalotine (Krx Kd = 2.10'11) andvoacamine (KrxKb= 1,3.10‘11). At pH 3,0, are eluted heyneamine (KrxKb= 5.10'12)adn voacristine (Krx Kb= 3,5.10'12). At pH 2,6, conopharyngine (Krx Kb= 2.10'12) iseluted, and finally, at pH 2,2, coronaridine (Krx Kb= 8.10"13) and vocagine(Krx Kb= 6.5.10'13) are eluted. By counter-current distribution in a bi-basic System of 20 dichloromethane, methanol and water 7/5/2 are obtained quaternary alkaloids, suchas 12-methoxy-Nb-methylvoacalotine and Nb-methylaffinisine under chloride form.
Kr représente the partition coefficient (aqueous phase/organic phaserépartition) and Kb is the dissociation constant. 25
Each alkaloid is purified by one or many new passages in recycling in acountercurrent distribution, and then by crystallization.
The alkaloids hâve been identified by 1H, 13C and mass spectrometry. 30
The measurements of voacamine in vitro IC5o are carried out as described inEXAMPLE 1. The results obtained are reported in Table 1, presented further. Thecytotoxicity of voacamine is the following : 011491 7 ED5o 3,8 μς/ΓηΙ for the cell lines of P 388 mice
ED50 13,6 pg /ml for the cell lines KB 5 EXAMPLE 3
We proceed like in Example 1, by using the bark of stem instead of the bark ofroot for obtaining a basic extract as described previously. The yield is of 1,9 %. 10 With this extract, we proceed in vitro to the measurements of IC50 as described in Example 1. The results are reported in the Table 1 below.
Table 1 IC50 Strains D6 Strains W2 Example 1 179 282 Example 2 238 290 Example 3 495 817
The values are expressed in ng/ml. The weaker they are, the more theproduct is active. We notice that voacamine présents a remarkable anti-Plasmodiumactivity against both types of strains (its activity being comparable to that of 20 chloroquine against the sensitive strains D6). The activity of the basic extract of thebark of stem from Example 3 is less, but nevertheless, this extract remains activeagainst the Plasmodium strains W2, which are résistant to chloroquine.
The most active is the basic extract of the tertiary alkaloids from Example 1, 25 obtained from the bark of roots. 8 011491 EXAMPLE 4
We proceed to clinical trials on a group of 74 persons in Mozambique, an 5 endemic région for Plasmodium strains résistant to chloroquine. These people areail afflicted with paludism.
We inject each person with 4 ml of the basic extract from Example 1, in 100 m,of physiological solution at the level of the 7th, 8th or 13th vertebrae. 10
After 3 hours, in most cases, the clinical signs of paludism (fever, vomiting,diarrhea, pain in the joints) hâve disappeared and after 4 hours, the cultures ofcorresponding cells are ail négative. 15 In 72% of the cases, the patients hâve recuperated in 4 hours and 90% of the patients hâve recuperated if the treatment is followed for three consecutive days.
Few patients hâve been treated orally (syrups) and anally to detect theeventual undesirable side effects. We hâve not noticed any. Therein lies a great 20 différence with the toxic side effects noticed with the usual médicaments used to fightpaludism in the régions of the world where mosquitoes hâve become immune tochloroquine.
Claims (13)
- 9 011491 CLAIMS1. Voacamine as an anti-malarial agent active against Plasmodium falciparumstrains, including the résistant strains. 5
- 2. Anti-malarial agent having an activity against the Plasmodium strains, includingthe résistant strains, characterised in that it comprises as a principal active agent,voacamine according to claim 1.
- 3. Anti-malarial agent according to claim 2, characterised in that it is in the form of a basic plant extract comprising voacamine.
- 4. Anti-malarial agent according to claim 3, characterised in that the basic extractis an extract from the Peschiera. 15
- 5. Agent according to claim 4, characterised in that the extract is an extract from thePeschiera Fuchsiaefolia.
- 6. Agent according to claim 5, characterised in that the basic extract is an extract 20 from the bark, more particularly from the bark of root of the Peschiera Fuchsiaefolia.
- 7. Anti-malarial agent according to claim 4, 5 or 6, characterised in that the basicextract is a fraction rich in tertiary alkaloids.
- 8. Anti-malarial agent according to claim 5, 6 or 7, characterised in that it comprises along with voacamine at least one alkaloid selected from the group consisting ofperivine, 16-epi-affinise, affirine, Nb-demethylvoacamine, vobasine, voachalotine,heynanine, voacristine, voacangerine, conopharyngine, coronaridine andvoacangine. 30
- 9. Anti-malarial drug active against Plasmodium falciparum strains, including therésistant strains, characterised in that it comprises voacamine according to claim 1,or one of its physiologically acceptable salts, associated to a physiologicallyacceptable support or excipient. 011491 10
- 10. Anti-malarial drug active against Plasmodium falciparum strains, including therésistant strains, characterised in that it comprises an anti-malarial agent according toany one of daims 2 to 8, in a free bases form or in a physiologically acceptable salts 5 form, associated to a physiologically acceptable support or excipient.
- 11. Process of isolation of an anti-malarial agent according to any one of daims 3 to7, characterised by the fact that it comprises the steps of : 10 - treating with a dilute acid a dry ground material of Pescheria Fuchsiaefolia or a part of said plant to only extract the basic principles, - alcalinizing the aqueous extract obtained therefrom to a pH of the order of 9,and 15 - extracting a fraction rich in tertiary alkaloids with an organic solvent, such asdichloromethane.
- 12. Process of isolation of voacamine from the basic extract according to daim 11, by20 counter-current distribution between an aqueous phase and an organic phase by varying the pH of the aqueous phase by successive levels, voacamine beingrecuperated at pH 3,2.
- 13. Process of isolation according to daim 12, characterised in that the stârting plant25 is a plant of the Pescheria genus, more particularly Pescheria Fuchsiaefolia.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT98TO000264A ITTO980264A1 (en) | 1998-03-26 | 1998-03-26 | APPLICATION OF A NON-QUATERNARY BASIC EXTRACT OF FUCHSIAEFOLIA PESCHIERA WITH ANTI-MALARICA ACTIVITY |
Publications (1)
Publication Number | Publication Date |
---|---|
OA11491A true OA11491A (en) | 2004-05-07 |
Family
ID=11416637
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
OA1200000261A OA11491A (en) | 1998-03-26 | 2000-09-22 | Voacamine as anti-malarial agent and anti-malarialagent containing voacamine. |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP1067938A1 (en) |
JP (1) | JP2002507570A (en) |
AP (1) | AP2000001926A0 (en) |
AU (1) | AU2742799A (en) |
BR (1) | BR9909153A (en) |
CA (1) | CA2325879A1 (en) |
IT (1) | ITTO980264A1 (en) |
OA (1) | OA11491A (en) |
WO (1) | WO1999048501A1 (en) |
ZA (1) | ZA200006020B (en) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2812199A1 (en) * | 2000-07-31 | 2002-02-01 | Maximun Frederic Yanze | Effervescent antimalarial compositions containing chloroquine, optionally other active agents, effervescent couple and taste modifiers, is dissolved in water to give a pleasant tasting solution for oral administration |
EP1491197A1 (en) * | 2003-06-26 | 2004-12-29 | Bertelli Motta, Guiseppe | Pharmaceutical composition comprising voacamine for the stimulation and modulation of the human immunologic system |
US20070232588A1 (en) * | 2004-09-15 | 2007-10-04 | Leonard Stella | Anti-parasitic and/or anti-viral and/or anti-microbial compositions |
US20070032460A1 (en) * | 2005-08-04 | 2007-02-08 | Leonard Stella | Use of voacamine and related compounds in the treatment of malaria |
CA2624750C (en) | 2005-10-04 | 2012-01-03 | The Director General, Defence Research And Development Organisation | Anti-malarial compound isolated from gomphostemma niveum |
EP1958638A1 (en) | 2007-02-14 | 2008-08-20 | Polichem S.A. | Use of chitosans to increase nail growth rate |
WO2013081374A1 (en) | 2011-11-28 | 2013-06-06 | 연세대학교 산학협력단 | Pharmaceutical composition for inhibiting angiogenesis containing plant-derived natural compound |
WO2014098877A1 (en) * | 2012-12-20 | 2014-06-26 | Demerx, Inc. | Substituted noribogaine |
GB2571696B (en) | 2017-10-09 | 2020-05-27 | Compass Pathways Ltd | Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced |
AU2020259406A1 (en) | 2019-04-17 | 2021-11-04 | Compass Pathfinder Limited | Treatment of depression and other various disorders with psilocybin |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2823204A (en) * | 1956-03-30 | 1958-02-11 | Gobey Lab | Alkaloids of voacanga |
-
1998
- 1998-03-26 IT IT98TO000264A patent/ITTO980264A1/en unknown
-
1999
- 1999-03-25 WO PCT/IB1999/000524 patent/WO1999048501A1/en not_active Application Discontinuation
- 1999-03-25 CA CA002325879A patent/CA2325879A1/en not_active Abandoned
- 1999-03-25 AP APAP/P/2000/001926A patent/AP2000001926A0/en unknown
- 1999-03-25 EP EP99907808A patent/EP1067938A1/en not_active Withdrawn
- 1999-03-25 JP JP2000537549A patent/JP2002507570A/en active Pending
- 1999-03-25 AU AU27427/99A patent/AU2742799A/en not_active Abandoned
- 1999-03-25 BR BR9909153-4A patent/BR9909153A/en not_active Application Discontinuation
-
2000
- 2000-09-22 OA OA1200000261A patent/OA11491A/en unknown
- 2000-10-26 ZA ZA200006020A patent/ZA200006020B/en unknown
Also Published As
Publication number | Publication date |
---|---|
AP2000001926A0 (en) | 2000-09-30 |
JP2002507570A (en) | 2002-03-12 |
WO1999048501A9 (en) | 2000-03-16 |
BR9909153A (en) | 2000-11-14 |
EP1067938A1 (en) | 2001-01-17 |
AU2742799A (en) | 1999-10-18 |
ITTO980264A1 (en) | 1999-09-26 |
CA2325879A1 (en) | 1999-09-30 |
ZA200006020B (en) | 2001-06-25 |
WO1999048501A1 (en) | 1999-09-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Ma et al. | The lycopodium alkaloids | |
Schiff | Opium and its alkaloids | |
KR102078204B1 (en) | Compositions and methods for joint health | |
Kacprzak | Chemistry and biology of Cinchona alkaloids | |
Zirihi et al. | Isolation, characterization and antiplasmodial activity of steroidal alkaloids from Funtumia elastica (Preuss) Stapf | |
Rubio-Piña et al. | Pharmaceutical applications of the benzylisoquinoline alkaloids from Argemone mexicana L. | |
Falodun et al. | Isolation of antileishmanial, antimalarial and antimicrobial metabolites from Jatropha multifida | |
OA11491A (en) | Voacamine as anti-malarial agent and anti-malarialagent containing voacamine. | |
WO2008099426A1 (en) | A composition for selective serotonin reuptake inhibition and process thereof | |
Adzhar Kamarulzaman et al. | Derivatives of Pheophorbide‐a and Pheophorbide‐b from Photocytotoxic Piper penangense Extract | |
US6858648B2 (en) | Laetispicine and laetispicine analogues, methods of use and preparation | |
Nautiyal | Natural products from plant, microbial and marine species | |
Basak | Cerpegin alkaloid and its analogues: chemical synthesis and pharmacological profiles | |
KR100440607B1 (en) | Pregnan glycoside compounds and preventives and remedies of neurodegenerative disease containing them as active ingredients | |
EP2712615B1 (en) | Composition containing arylnaphthalene lignan derivative for preventing and/or treating dementia | |
MXPA00009370A (en) | Voacamine as anti-malarial agent and anti-malarial agent containing voacamine | |
Hikal et al. | Cissampelos pareira: a potential source of medicine to treat malaria. | |
CN109715594A (en) | As decolorising agent or the difluorizated compound of brilliant white agent | |
Kumbhar et al. | Huperzine a from Huperzia serrata-a systematic review | |
Hassan et al. | Alkaloids: A Continuation of Search for Antimalarial Leads | |
Yue | Studies on Chemical Constituents And Biological Activities of Nauclea officinalis and Nauclea subdita | |
Nwambie et al. | Preliminary studies on some Nigerian herbal purgative recipes | |
Dank | Synthesis of Novel Antimalarials | |
OMITOLA | MOLECULAR AND BIOLOGICAL STANDARDISATION OF Alstonia boonei DE WILD. AND Alstonia congensis ENGL. LEAVES AND STEM-BARKS | |
JP2005206501A (en) | Antimalarial composition comprising flavonoid c-glycoside as active ingredient |