squamocin and isomurisolenin

The active compounds obtained from some medicinal plants used traditionally worldwide for the treatment of leishmaniasis are reviewed. Among these active molecules, described in recent literature are quinoline alkaloids such as alkyl-2 quinoline and aryl-2 quinoline from Galipea longiflora, isoquinoline alkaloids such as isoguattouregidine from Guatteria foliosa, indole alkaloids such as conodurine and gabunine from Pescheiera van heurkii, terpenes such as jatrogrossidione from Jatropha grossidentata, acetogenins such as senegalene from Annona senegalensis and lignans such as (+)nyasol from Asparagus africanus. Other natural compounds with antileishmanial activity are coumarins, chalcones, lactones, tetralones and saponins. Some of them are known antiprotozoal natural products. These compounds could be used as templates to discover new and effective drugs against leishmaniasis.

Topics: Alkaloids; Animals; Antiprotozoal Agents; Chalcone; Chalcones; Coumarins; Drug Evaluation, Preclinical; Furans; Lactones; Leishmania; Leishmaniasis; Molecular Structure; Phytotherapy; Plant Extracts; Plants, Medicinal; Quinones; Terpenes

Several glycosyl derivatives of squamocin (1) have been synthesized by glycosylation under Lewis acid catalysis with two different 1-O-acetyl sugars. Separation of these compounds has been achieved by HPLC and centrifugal partition chromatography (CPC). A detailed NMR, ESIMS, and LSIMS study allowed complete structural elucidations. The cytotoxic activity of the glycosyl derivatives was investigated and compared with that of squamocin and dihydrosquamocin against human epidermoid carcinoma cells (KB), African green monkey (Cercopithecus aethiops) kidney epithelial cells (VERO), and mouse lymphocytic leukemia cells (L1210). The antiproliferative effects of some derivatives were studied on cell cycles in mouse lymphocytic leukemia cells (L1210).

Topics: Animals; Antineoplastic Agents; Cell Cycle; Chlorocebus aethiops; Drug Screening Assays, Antitumor; Furans; Glycosylation; Humans; Lactones; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Tumor Cells, Cultured; Vero Cells

The acetogenins of Annonaceae are known by their potent cytotoxic activity. In fact, they are promising candidates as a new future generation of antitumoral drugs to fight against the current chemiotherapic resistant tumors. The main target enzyme of these compounds is complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, a key enzymatic complex of energy metabolism. In an attempt to characterize the relevant structural factor of the acetogenins that determines the inhibitory potency against this enzyme, we have prepared a series of bis-tetrahydrofuranic acetogenins with different functional groups along the alkyl chain. They comprise several oxo, hydroxylimino, mesylated, triazido, and acetylated derivatives from the head series compounds rolliniastatin-1, guanacone, and squamocin. Our results suggest a double binding point of acetogenins to the enzyme involving the alpha,alpha'-dihydroxylated tetrahydrofuranic system as well as the alkyl chain that links the terminal alpha, beta-unsaturated-gamma-methyl-gamma-lactone. The former mimics and competes with the ubiquinone substrate. The latter modulates the inhibitory potency following a complex outline in which multiple structural factors probably contribute to an appropriate conformation of the compound to penetrate inside complex I.

Topics: Animals; Antineoplastic Agents; Cattle; Electron Transport Complex I; Enzyme Inhibitors; Furans; In Vitro Techniques; Lactones; Mitochondria; NADH, NADPH Oxidoreductases; Structure-Activity Relationship