Falciparum W2 Strain Research Articles

Phytochemical, Antiparasitic and Antimicrobial Investigations of Terminalia brownii

Terminalia brownii is an African medicinal plant used to treat parasitic and microbial infections [1]. Chromatographic separations on the stem bark extract aimed at identifying the active components led to isolation of a new oleanane-type triterpenoid, along with seven known oleanane-type triterpenoids and seven ellagic acid derivatives. The new compound was identified using spectroscopic methods as 3β,24-O-ethylidenyl-2α,19α-dihydroxyolean-12-en-28-oic acid (1). The compounds were evaluated for their antiplasmodial, antileishmanial and antimicrobial activities giving the most potent antiplasmodial activity with IC50 values of 2.76 µg/mL for 23-galloylarjunolic acid (2) against P. falciparum W2 strain and the most potent antimicrobial activity with IC50 values of 0.32 µg/mL for diellagic lactone (3) against C. glabrata.

Antimalarial Activity of Cocos nucifera Husk Fibre: Further Studies.

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25–500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles.

Design, synthesis and evaluation of 3-methylene-substituted indolinones as antimalarials

The design, synthesis and evaluation of 3-methylene-substituted indolinones as falcipain inhibitors and antiplasmodial agents are described. These compounds react readily with thiols via an addition-elimination mechanism, indicating their potential as cysteine protease inhibitors. Several indolinones containing a Leu-i-amyl recognition moiety were found to be moderate inhibitors of the Plasmodium falciparum cysteine protease falcipain-2, but not of the related protease falcipain-3, and displayed antiplasmodial activity against the chloroquine-resistant P. falciparum W2 strain in the low micromolar range. Coupling a 7-chloroquinoline moiety to the 3-methylene-substituted indolinone scaffold led to a significant improvement in antiplasmodial activity.

Bis-alkylamine quindolone derivatives as new antimalarial leads

Quindolone derivatives, designed to target the malaria parasite digestive vacuole and heme detoxification pathway, have been synthesized by reaction with 2-chloro- N, N-diethylethanamine. This reaction gave N,O-, N,N- and O-alkylated products containing one or two basic side-chains. The compounds were evaluated for antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum W2 strain and for cytotoxicity in HepG2 A16 hepatic cells. By incorporating alkylamine side chains and chlorine atoms in the quindolone nucleus we transformed the inactive tetracyclic parent quindolones into moderate or highly active and selective antimalarial compounds. The most active and selective compound, 5c, showed an IC 50 = 51 nM for P. falciparum and a selectivity ratio of 98.

Evaluation of the potential of the marine sponges of the Zanzibar Island to yield antimalarial and antimicrobial active compounds

Background: Emergence of new and re-emergence of old infections continue to elude prospects of reducing morbidity and mortality caused by microbial infections. Trends of resistance to currently in use antimicrobials and antimalarials threaten to increase mortality caused by these infections. This study explores the potential of marine invertebrates as a source for new antimicrobials and antimalarials. Methods: The lactate dehydrogenase method was used to assay marine sponges for activity against Plasmodium falciparum, while the disc diffusion method was used to assay the extracts for antibacterial and antifungal activity. Results: Extracts of some marine sponges from the Zanzibar Island exhibited both antiplasmodial and antimicrobial activities. Among the 55 marine sponge extracts that were tested 23 (41.8%) inhibited Plasmodium falciparum W2 strain by more than 50% at both 250 and 50 µg/ml concentrations. Moderate polar extracts were more active against Plasmodium falciparum W2 strain than polar and non-polar extracts. None of the 12 extracts that were tested on Plasmodium falciparum strain D6 exhibited inhibitory activity reaching 50%. Among 18 marine sponge extracts that were tested for antimicrobial activity 12 (66.7%) showed activity against one or more of the bacteria and fungi used ranging from weak to strong on an arbitrary criterion. The ethyl acetate extracts of Agelas mauritania and Oceanopia sp. exhibited high activity against the fungi Candida albicans and Cryptococcus neoformans. The best antibacterial profile was exhibited by ethyl acetate extracts of Aplysinopsis sp., Halichondrida sp. 1 and Oceanopia sp. Conclusion: These results support the need for intensified efforts to search for active antimalarial and antimicrobial compounds from the Zanzibar marine sponges.

Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition

A series of artemisinin–vinyl sulfone hybrid molecules with the potential to act in the parasite food vacuole via endoperoxide activation and falcipain inhibition was synthesized and screened for antiplasmodial activity and falcipain-2 inhibition. All conjugates were active against the Plasmodium falciparum W2 strain in the low nanomolar range and those containing the Leu-hPhe core inhibited falcipain-2 in low micromolar range.

Cryptolepine analogues containing basic aminoalkyl side-chains at C-11: Synthesis, antiplasmodial activity, and cytotoxicity

A series of cryptolepine derivatives has been synthesized through the incorporation of short basic side-chains in the C-11 position of the 10H-indolo[3,2-b]quinoline scaffold. Their antiplasmodial activity was evaluated in vitro against the chloroquine resistant Plasmodium falciparum W2 strain, showing IC(50) values between 22 and 184 nM, while their cytotoxicity was assessed using HUVEC cells, revealing three compounds with a selectivity ratio higher than 10. The most selective of these derivatives, 4d, with a selectivity ratio of 46, was also the least cytotoxic of the series.

Anti-plasmodial and Cholinesterase Inhibiting Activities of some Constituents of Psorospermum glaberrimum

Glaberianthrone (1), a new bianthrone was isolated from the hexane extract of the stem bark of Psorospermum glaberrimum together with thirteen known compounds: 3-geranyloxyemodin anthrone (2), friedelan-3-one (3), 3-prenyloxyemodin anthrone (4), 3-geranyloxyemodin (5), 3-prenyloxyemodin (6), friedelan-3-ol (7), acetylvismione D (8), betulinic acid (9), 2-geranylemodin (10), bianthrone A2b (11), bianthrone 1a (12), emodin (13) and 2-prenylemodin (14). The structures of the isolated compounds were established by means of spectroscopic methods. The extracts and the isolated compounds were tested in vitro for their anti-plasmodial activity against Plasmodium falciparum (chloroquine resistant strain W2) and for their acetyl- and butyrylcholinesterase inhibitory properties. The n-hexane extract showed good anti-plasmodial activity against P. falciparum W2 strain, with IC(50) of 0.87 microg/ml. It also exhibited 65.5% and 98.2% of acetyl- and butyrylcholinesterase inhibition at 0.2 mg/ml, respectively. Compounds 2 and 8 showed the best potencies against P. falciparum W2 strain with IC(50) of 1.68 microM and 0.12 microM, (0.66 microg/ml and 0.054 microg/ml) respectively. All tested compounds showed good butyrylcholinesterase inhibition activities with compound 12 displaying the best potency (IC(50) 9.25+/-0.25 microM). All the tested compounds showed weak inhibitory activity against acetylcholinesterase.

Anti- Pneumocystis carinii and antiplasmodial activities of primaquine-derived imidazolidin-4-ones

A series of primaquine-derived imidazolidin-4-ones were screened for their in vitro activity against Pneumocystis carinii and Plasmodium falciparum W2 strain. Most compounds were active against P. carinii above 10 μg/mL and displayed slight to marked activity. The imidazolidin-4-ones most active against P. carinii were also those most active antiplasmodial agents, in the μM range. One of the tested imidazolidin-4-ones was slightly more active than the parent primaquine and may represent a lead compound for the development of novel anti- P. carinii 8-aminoquinolines with increased stability and resistance to metabolic inactivation.

Antimalarial activity in crude extracts of some Cameroonian medicinal plants

Fifteen crude extracts from the stem bark and seeds of four medicinal plants, viz: Entandrophragma angolense, Picralima nitida, Schumanniophyton magnificum and Thomandersia hensii were tested in vitro for their antimalarial activity against the chloroquine-resistant Plasmodium falciparum W2 strain. The results showed that the extracts of these plants possessed some antimalarial activity, the methanol extract of Picralima nitida demonstrating the highest activity in vitro. Further isolation and identification of some active compounds from these plants will justify their common use in traditional medicine for the treatment of malaria or fever in Cameroon.