benzofurans and Parasitemia

To find out the in vitro antiplasmodial activities of mangrove leaf extracts.. In vitro antiplasmodial assay was carried out with 13 different mangrove plants. Column chromatography was performed with the most potent Agecerious corniculatum (A. corniculatum) by using various solvent extractions. GC-MS was also preformed with the most potent ethanolic fraction of the A. corniculatum extract.. Of the 13 mangroves plants, A. corniculatum showed maximum percentage of parasitemia suppression (94.98 ± 1.16)%. Column chromatography was performed with A. corniculatum with different solvents and the methanolic extract showed maximum percentage (99.73±1.63)% of parasitemia inhibition at 150 μg/mL concentration with the IC(50) value of (29.28±3.23) μg/mL concentration. The results of the GC-MS analysis observed that, the most potent methanolic extract showed maximum retention time (30.687 RT) and the chemical class was identified as Spiro [benzofuran-2(3 H), 1'(3 cyclohexane)-2',3-dione, 7-chloro-4',6] which was responsible for the antiplasmodial activity.. It is concluded from the present study that, the chemical constituents of A. corniculatum collected from Pichavaram mangrove forest can be used as a putative antiplasmodial drugs in future.

Topics: Antimalarials; Benzofurans; Chromatography; Erythrocytes; Humans; Malaria, Falciparum; Parasitemia; Parasitic Sensitivity Tests; Phytotherapy; Plant Extracts; Plant Leaves; Plasmodium falciparum; Primulaceae

There is an urgent need for new anti-malarial drugs to combat the resurgence of resistance to current therapies. To exploit the A/T richness of malaria DNA as a potential target for anti-malarial drugs we tested an A/T-specific DNA synthesis inhibitor, adozelesin, for activity against Plasmodium falciparum in vitro and Plasmodium chabaudi adami in mice. Adozelesin is a DNA alkylating agent that exhibits specificity for the motif A/T, A/T and A. In P. falciparum 3D7 cultures, adozelesin acts as a powerful inhibitor of parasite growth (IC(50) of 70 pM) and is equally potent at killing the drug-resistant strains FCR3 and 7G8. Using a real-time PCR assay, we show that treatment with adozelesin in vitro results in damage of P. falciparum genomic DNA. In synchronized cultures, adozelesin exhibits a concentration-dependent effect on parasitemia and on the development of parasites through the asexual cycle. In asynchronous cultures, parasites arrest at all stages of the asexual cycle suggesting that adozelesin exerts other anti-parasitic effects in addition to inhibiting DNA replication. These anti-parasite effects are irreversible since cultures exposed to adozelesin for more than 6h fail to recover upon removal of the drug. Furthermore, adozelesin is very effective at suppressing malaria infection in vivo; growth of P. c. adami DK in mice was highly impaired by a single injection of adozelesin (25 microg/kg) at 4 days post-infection. These results demonstrate that adozelesin irreversibly blocks parasite growth in vitro and suppresses parasite infection in vivo, suggesting that A/T-specific DNA damaging agents represent a new class of compounds with potential as anti-malarials.

Topics: Adenine; Animals; Antimalarials; Base Pairing; Benzofurans; Cyclohexanecarboxylic Acids; Cyclohexenes; DNA, Protozoan; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Duocarmycins; Female; Indoles; Injections, Intraperitoneal; Malaria, Falciparum; Mice; Mice, Inbred BALB C; Parasitemia; Plasmodium falciparum; Thymine