Diterpene formamides from the tropical marine sponge Cymbastela hooperi and their antimalarial activity in vitro.

Further investigations of the VLC (vacuum-liquid chromatography) fractions obtained from the dichloromethane solubles of the tropical marine sponge Cymbastela hooperi led to the isolation and characterization of five new diterpene formamides, 1-5. Compound 1 is one of the very few examples of a natural product that contains both formamide and isonitrile functionalities within the same molecule. In in vitro antiplasmodial bioassays, 1 was found to have moderate activity (IC(50) 0.

Potential antimalarial lead structures from fungi of marine origin.

Antiplasmodial and cytotoxicity testing of five highly oxygenated natural products (6R,12R,14R-colletoketol, 6R,11R,12R,14R-colletoketodiol, dihydrobotrydial, pycnidione, and 3R,4S-hydroxymellein), all derived from fungi of marine origin, showed one of them, pycnidione, to have activities against three different strains of Plasmodium falciparum in the sub-micromolar (microM) range. Although the mean selectivity index of 1 for the observed antiplasmodial activity of 4 is low, pycnidione's usefulness as a potential lead structure should not be ignored.

Cis and trans factors involved in apicoplast targeting in Toxoplasma gondii.

Ribosomal subunit protein 9 (rps9) is a nuclearly encoded protein that resides in the apicoplast organelle of Toxoplasma gondii. Two cis-acting regions within the rps9 transit domain (amino acids 38-49 and 79-86), when combined with the rps9 signal sequence, were necessary and sufficient for apicoplast targeting. To investigate proteins interacting with the rps9 leader sequence, parasites expressing rps9 leader constructs fused to a glutathione S-transferase (GST) reporter were prepared, and proteins associated with the leader constructs were purified from extracts by affinity chromatography.

Analysis of apicoplast targeting and transit peptide processing in Toxoplasma gondii by deletional and insertional mutagenesis.

Deletion and insertion mutagenesis was used to analyze the targeting sequence of the nuclear encoded apicoplast protein, the ribosomal protein small subunit 9 of Toxoplasma gondii. Previous studies have shown that nuclear encoded apicoplast proteins possess bipartite leaders having characteristic signal sequences followed by serine/threonine rich transit sequences. Deletion analysis demonstrated that the first 55 amino acids of the rps9 leader were sufficient for apicoplast targeting.

Plasmodium falciparum: the effects of atovaquone resistance on respiration.

Atovaquone is an antimalarial agent that specifically inhibits the cytochrome bc(1) complex of the cytochrome pathway. High-level atovaquone resistance is associated with a point mutation in the cytochrome b gene. A pair of isogenic clinical isolates of Plasmodium falciparum derived from before and after the acquisition of atovaquone resistance was used to determine whether the change in the cytochrome b gene resulted in changes in respiration in response to atovaquone.