ABSTRACT
The appearance of drug resistant Plasmodium falciparum malaria necessitates the search for novel antimalarial agents. Using the classical ring-bioisosterism concept as a strategy to develop new potential drugs, 1H-pyrazolo[3,4-b]pyridine 4-aminomethanol compounds were designed and synthesized as isosteres of the classical quinoline antimalarial mefloquine. The hydrochloride form of these compounds were tested for in vitro antimalarial activity against chloroquine-sensitive (Sierra Leone D-6) and resistant (Indochina W-2) clones of P. falciparum. The results described herein indicated that 1-H-pyrazolo[3,4-b]pyridine system represents a bioisosteric framework to quinoline system in the antimalarial activity.
Subject(s)
Antimalarials/chemical synthesis , Plasmodium falciparum/drug effects , Pyridines/chemical synthesis , Animals , Antimalarials/pharmacology , Antimalarials/toxicity , Chlorocebus aethiops , Chloroquine/pharmacology , Pyridines/pharmacology , Pyridines/toxicity , Vero CellsABSTRACT
A new quassinoid, 11-O-trans-p-coumaroyl amarolide (1) was isolated from Castela texana, and the structure was elucidated by spectroscopic analysis. Compound 1 is the first coumaroyl quassinoid derivative to have been isolated from nature. The known compounds amarolide (2), chaparrinone, chaparrin, glaucarubolone, holacanthone, and 15-O-beta-D-glucopyranosyl glaucarubol were also isolated. All isolated compounds were tested for their cytotoxicity and antiprotozoal activities.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antiprotozoal Agents/isolation & purification , Plants, Medicinal/chemistry , Triterpenes/isolation & purification , Animals , Antimalarials/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antiprotozoal Agents/pharmacology , Giardia/drug effects , Mexico , Plasmodium falciparum/drug effects , Texas , Triterpenes/pharmacology , Trypanocidal Agents/pharmacology , Tumor Cells, CulturedABSTRACT
Two antimalarial quassinoids, gutolactone [1] and simalikalactone D [2], have been characterized by bioactivity-directed fractionation from the bark of Simaba guianensis collected near Manaus, Brazil. Compound 2 was previously isolated from Simaba multiflora and Quassia africana and shown to be an active antimalarial in vitro. This is the first occurrence of 1. The structure of the novel quassinoid was established by spectral methods including 2D nmr spectroscopy.