ABSTRACT
Malaria and cancer cause the death of millions of people every year. To combat these two diseases, it is important that new pharmaceutically active compounds have the ability to overcome multidrug resistance in cancer and Plasmodium falciparum strains. In search of effective anti-cancer and anti-malaria hybrids that possess improved properties compared to their parent compounds, a series of novel 1,2,4-trioxane-based hybrids incorporating egonol and/or ferrocene fragments were synthesized and tested in vitro against P. falciparum strains, CCRF-CEM cells and the multidrug-resistant P-glycoprotein-over-expressing CEM/ADR5000 cells. The most active compounds against P. falciparum strains were artesunic acid homodimers 12 and 13 (IC50 of 0.32 and 0.30 nM, respectively), whereas novel hybrids 7 (1,2,4-trioxane-ferrocene-egonol), 9 (1,2,4-trioxane-ferrocene) and 11 (artesunic acid-egonol) showed a remarkable cytotoxicity toward CCRF-CEM cells (IC50 of 0.07, 0.25 and 0.18 µM, respectively). A cooperative and synergistic effect of the three moieties 1,2,4-trioxane, ferrocene and egonol in hybrid molecule 7 is significant and is obviously stronger than in hybrids 9 (1,2,4-trioxane-ferrocene) and 11 (artesunic acid-egonol), which comprises of only two of the three considered parent compounds. Interestingly, hybrid 9 containing a 1,2,4-trioxane and a ferrocene fragment has shown to be the most effective among the studied hybrids against the tested multidrug-resistant leukemia CEM/ADR5000 cells (IC50 of 0.57 µM) and possesses a degree of cross-resistance of 2.34.
Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm/drug effects , Leukemia/drug therapy , Plasmodium falciparum/drug effects , Antimalarials/chemical synthesis , Antineoplastic Agents/chemical synthesis , Benzofurans/chemical synthesis , Benzofurans/chemistry , Benzofurans/pharmacology , Cell Lineage , Drug Resistance, Multiple/drug effects , Ferrous Compounds/chemical synthesis , Ferrous Compounds/chemistry , Ferrous Compounds/pharmacology , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacology , Humans , Malaria, Falciparum/drug therapy , MetallocenesABSTRACT
From the whole plant of Astragalus halicacabus (Sect. Halicacabus), a new cycloartane-type glycoside, (20R,24S)-3-O-[α-L-arabinopyranosyl-(1â2)-ß-D-xylopyranosyl]-20,24-epoxy-16-O-ß-D-glucopyranosyl-3ß,6α,16ß,25-tetrahydroxycycloartane, and a new glycoside, 3-O-[ß-D-apiofuranosyl-(1â2)-ß-D-glucopyranosyl]maltol were isolated together with seven known cycloartane-type glycosides, i.e., cyclocanthoside D, askendosides D, F, and G, cyclosieversioside G, cyclostipuloside A, elongatoside, and a known maltol glucoside, 3-O-ß-D-glucopyranosylmaltol. The structures were elucidated by means of high-resolution mass spectrometry, and extensive 1D- and 2D-NMR spectroscopic analysis. This is the first phytochemical work on A. halicacabus, and a maltol glycoside was encountered for the first time in the Leguminosae family.
Subject(s)
Astragalus Plant/metabolism , Cyclohexanones/chemistry , Disaccharides/chemistry , Glycosides/chemistry , Astragalus Plant/chemistry , Cyclohexanones/isolation & purification , Disaccharides/isolation & purification , Glycosides/isolation & purification , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Triterpenes/chemistryABSTRACT
Eighteen derivatives of egonol (A-R) were synthesized and evaluated for their antimicrobial activities against Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 6633, Candida albicans ATCC 10231 and Escherichia coli ATCC 8739 microorganisms comparing with egonol. The obtained data reported that compound B exhibited improved activities against all tested bacteria than egonol, others have shown different range of activities.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Benzodioxoles/chemical synthesis , Benzofurans/chemical synthesis , Styrax , Sulfuric Acid Esters/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Bacillus subtilis/drug effects , Benzodioxoles/chemistry , Benzodioxoles/pharmacology , Benzofurans/analysis , Candida albicans/drug effects , Escherichia coli/drug effects , Microbial Sensitivity Tests , Molecular Structure , Seeds , Staphylococcus aureus/drug effects , Structure-Activity Relationship , Sulfuric Acid Esters/chemistry , Sulfuric Acid Esters/pharmacologyABSTRACT
Synthesis of egonol derivatives, 5-(3''-chloropropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 1, 5-(3''-bromopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 2, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propanal 3, 5-(3''-iodopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 4, 5-[3-(3''-bromopropyloxy) propyl]-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 5, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylmethanoate 6, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propyloleate 7, 5-[3''-hydroxypropyl]-6-bromo-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 8, 4-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]butanenitrile 9, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylbenzoate 10, 5-[3''-hydroxypropyl]-7-methoxy-3-nitro-2-(3',4'-methylenedioxyphenyl)benzofuran 11 and their antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli are reported. The starting material egonol 5-[3''-(hydroxy)propyl]-7-methoxy-2-(3', 4'methylenedioxyphenyl)benzofuran was isolated from seeds of Styrax officinalis L. The structural elucidication of these compounds (1-11) was established using 1D ((1)H, (13)C), 2D NMR (HMBC, HMQC, COSY) and LCMS spectroscopic data. While egonol and some synthesised new compounds show similar antibacterial activity and MIC values against S. aureus, B. subtilis, C. albicans and E. coli, other new derivatives show different activity against S. aureus, B. subtilis, C. albicans and E. coli.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Benzofurans/chemical synthesis , Benzofurans/pharmacology , Anti-Bacterial Agents/chemistry , Bacillus subtilis/drug effects , Benzofurans/chemistry , Escherichia coli/drug effects , Magnetic Resonance Spectroscopy , Molecular Structure , Staphylococcus aureus/drug effects , Structure-Activity RelationshipABSTRACT
A new benzofuran was isolated from seeds of Styrax officinalis and has been identified as 5-[3"-(2-methylbutanoyloxy) propyl]-7-methoxy-2-(3',4'-dimethoxyphenyl) benzofuran (1) by means of spectroscopic analysis.
Subject(s)
Benzofurans/chemistry , Phytotherapy , Plant Extracts/chemistry , Styrax , Humans , Magnetic Resonance Spectroscopy , SeedsABSTRACT
The benzofuran constituents of the seeds of Styrax officinalis were investigated. From the hexane extract, two new constituents named 5-(3"benzoyloxypropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran (5) and 4-[3"-(1c-methylbutanoyloxy)propyl]-2-methoxy-(3',4'-methylenedioxyphenyl)-1a, 5b-dihydrobenzo-[3,4]-cyclobutaoxirene (6) were isolated together with four known compounds, 5-[3"-(1c-methylbutanoyloxy)propyl]-7-methoxy-2-(3',4'-dimethoxyphenyl)-benzofuran (4), 5-[3"-(1c-methylbutanoyloxy)propyl]-7- methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran (3), 5-(3"-acetoxypropyl)-7-methoxy2-(3',4'-methylenedioxphenyl)-benzofuran (2) and 5-(3"-hydroxypropyl)-7-methoxy-2-(3',4'-met hylenedioxyphenyl)-benzofuran (1). Although the compounds 1, 2, and 3 have been isolated previously from the seeds of Styrax obassia, this is the first record of their isolation from seeds of Styrax officinalis. The structures of the isolated compounds were established by 1D- and 2D-NMR (HMBC, HMQC, COSY), FABMS and high-resolution ESI FTMS.
Subject(s)
Benzofurans/isolation & purification , Styrax/chemistry , Benzofurans/chemistry , Mass Spectrometry , Nuclear Magnetic Resonance, Biomolecular , Plants, Medicinal/chemistry , Seeds/chemistryABSTRACT
Three triterpene saponins named Styrax-saponin A-C (1-3) were found in pericarps of Styrax officinalis together with the deacylsaponin (4). Structural determinations were achieved using 1D-, 2D-NMR and mass spectrometry.
