ABSTRACT
Two lupane and hopane caffeates (1 and 4) and two hopane coumarates (2 and 3) along with eight known compounds (5-12) were isolated from stems and roots of Lepisanthes senegalensis. Their structures were established on the basis of spectroscopic techniques. The structure of compound 2 was confirmed by single-crystal X-ray diffraction analysis. Triterpenes 1 and 4-6 showed cytotoxicity against the NCI-H187 cell line with IC50 values of 31.5, 28.5, 16.2, and 4.0 µM, respectively. However, these compounds also showed cytotoxicity against Vero cells, with IC50 values of 75.5, 16.6, 8.9, and 5.0 µM, respectively. In addition, compound 6 exhibited a moderate antimalarial activity with an IC50 value of 4.5 µM.
Subject(s)
Sapindaceae/chemistry , Triterpenes/pharmacology , Animals , Antimalarials/chemistry , Antimalarials/isolation & purification , Antimalarials/pharmacology , Carcinoma, Squamous Cell/drug therapy , Cell Line, Tumor , Chlorocebus aethiops , Crystallography, X-Ray/methods , Humans , Inhibitory Concentration 50 , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Roots/chemistry , Plant Stems/chemistry , Small Cell Lung Carcinoma/drug therapy , Triterpenes/chemistry , Triterpenes/isolation & purification , Vero Cells , X-Ray Diffraction/methodsABSTRACT
Astraodorol, a major lanostane-type triterpene isolated from the edible mushroom Astraeus odoratus, was subjected to chemical modifications. Ten derivatives have been synthesized and their biological activities were evaluated. Compounds 5, 6, 7a, 7c, 7e, 7f, and 7 g exhibited strong antimalarial activity with IC50 values of 4.85, 4.48, 4.16, 4.46, 3.45, 3.23, and 3.41 µg/mL, respectively. Compounds 7a, 7c, and 7e showed moderate cytotoxicity against NCI-H187 with IC50 values of 23.36, 34.28, and 9.84 µg/mL. Compound 7e demonstrated moderate cytotoxicity against KB, MCF-7, and Vero cell lines with IC50 values of 16.94, 49.60, and 26.48 µg/mL, respectively.
Subject(s)
Agaricales/chemistry , Antimalarials/chemical synthesis , Antineoplastic Agents/chemical synthesis , Triterpenes/chemical synthesis , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Chlorocebus aethiops , Humans , Inhibitory Concentration 50 , KB Cells , MCF-7 Cells , Molecular Structure , Plasmodium falciparum/drug effects , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacology , Vero CellsABSTRACT
The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the alpha- and beta-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each alpha-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya.
ABSTRACT
During the biosynthesis of certain tropane alkaloids, littorine (1) is rearranged to hyoscyamine (3). Recent evidence indicates that this isomerisation is a two-step process in which the first step is an oxidation/rearrangement to give hyoscyamine aldehyde (2). This step is catalysed by CYP80F1, a cytochrome P450 enzyme, which was recently identified from the plant Hyoscyamus niger; CYP80F1 also catalyses the hydroxylation of littorine at the 3'-position. The mechanisms of the reactions catalysed by CYP80F1 were probed with synthetic deutero and arylfluoro analogues of 1. Measurement of the primary kinetic isotope effects indicates that C3' hydrogen abstraction is the rate-limiting step for the oxidation/rearrangement of natural littorine, and for the 3'-hydroxylation reaction of the unnatural S enantiomer of littorine. The character of the intermediates in the oxidation/rearrangement and hydroxylation reaction was probed with the use of arylfluorinated analogues of (R)-littorine (natural stereoisomer) and (S)-littorine (unnatural stereoisomer) as substrates for CYP80F1. The relative conversions of ortho-, meta- and para-fluorolittorine analogues were used to obtain information on the likely intermediacy of either a benzylic radical or benzylic carbocation intermediate. The data suggest that hydroxylation takes place via a benzylic carbocation intermediate, whereas the product profile arising from rearrangement is more consistent with a benzylic radical intermediate.
Subject(s)
Alkaloids/biosynthesis , Atropine Derivatives/metabolism , Cytochrome P-450 Enzyme System/metabolism , Atropine/chemistry , Atropine/metabolism , Atropine Derivatives/chemistry , Biocatalysis , Fluorine/chemistry , Hydroxylation , Oxidation-Reduction , StereoisomerismABSTRACT
Three new azaphilones named rotiorinols A-C (1-3), two new stereoisomers, (-)-rotiorin (4) and epi-isochromophilone II (5), and a known compound, rubrorotiorin (6), were isolated from the fungus Chaetomium cupreum CC3003. Structures were established on the basis of spectroscopic evidence. The absolute configuration of 1 was determined by the modified Mosher's method along with an X-ray analysis of its acetate derivative, as well as by chemical transformation. Compounds 1, 3, 4, and 6 exhibited antifungal activity against Candida albicans with IC50 values of 10.5, 16.7, 24.3, and 0.6 microg/mL, respectively.
