24 research outputs found
Glycyrrhizin and glycyrrhetic acid: scaffolds to promising new pharmacologically active compounds
No full textGlycyrrhizinic acid (GL), also known as glycyrrhizin, is a triterpene saponin, a natural product found on the root of Glycyrrhyza glabra L. (“licquorice”), used worldwide as sweetener and in the traditional eastern medicines. This review is focused on a series of new derivatives synthesized using GL and its aglycon, glycyrrhetinic acid (GLA), as starting materials, the pharmacological activities described for those compounds, as well as new activities reported for GL and GLA themselves.O ácido glicirrizínico (GL), também conhecido como glicirrizina, é uma saponina triterpênica, um produto natural encontrado na raiz de Glycyrrhyza glabra L. (“licquorice” ou “alcaçuz”), utilizada mundialmente como edulcorante e também na medicina tradicional do Oriente. Este artigo de revisão enfoca os novos compostos sintetizados usando GL ou sua aglicona, o ácido glicirretínico (GLA), como materiais de partida e as atividades farmacológicas descritas para os mesmos e seus derivados
Conformational Characterization of Ipomotaosides and Their Recognition by COX-1 and 2
No full textThe aerial parts of Ipomoea batatas are described herein to produce four new resin glycosides, designated as ipomotaosides A, B, C, and D. Ipomotaoside A was found to present inhibitory activity on both cyclooxygenases. However, the conformational elucidation of these molecules may be difficult due to their high flexibility. In this context, the current work presents a conformational characterization of ipomotaosides A–D in aqueous and nonaqueous solvents. The employed protocol includes metadynamics evaluation and unrestrained molecular dynamics simulations (MD). The obtained data provided structural models for the ipomotaosides in good agreement with previous ROESY distances measured in pyridine. Accordingly, the most abundant conformation of ipomotaoside A in solution was employed in flexible docking studies, providing a structural basis for the compound’s inhibition of COX enzymes. The so-obtained complex supports resin glycosides’ role as original scaffolds for future studies, aiming at structural optimization and development of potential new anti-inflammatory agents
One-pot synthesis of secondary and tertiary amines from R(+)-limonene by tandem hydroformylation/reductive amination (hydroaminomethylation)
No full textIn this work, we were able to synthesize, in good isolated yields, seven R(+)-limonene derived amines (five of that described for the first time) employing a rhodium catalysed hydroaminomethylation reaction. This protocol consists in an one-pot three step reaction: double bond hydroformylation, aldehyde/amine condensation and imine/enamine hydrogenation. Hydroaminomethylation, besides the high yields, has a high atom economy because just 1 mol of water is wasted per mol of limonene. Due to our catalytic optimizations, the reaction time was reduced from 48 h (described in the literature) to 10-24 h, as well as limonene isomerization was strongly minimized by the triphenylphosphine added.</p
Molecular modeling studies of the acridinones series.
No full text(A), steric complementarity between the colchicine site and S-7 (B), binding mode of S-11 showing a hydrogen bond between the NH groups of acridinones and Thr α179 (C), binding mode of S-10 where the trimethoxybenzyl group occupies the hydrophobic pocket of the colchicine site (D), docking pose for S-7 with a hydrogen bond between the NO2 group and Leu β252 (E), docking pose for S-6 with a hydrogen bond between oxygen from dioxalane and Cys β241 (F), Comparison of predicted interactions between the docking pose of S-7 and the crystal structure of tubulin (PDB ID: 1SA0) and the predicted interactions between crystallographic DAMA-colchicine (PDB ID: CN2) and tubulin (PDB ID: 1SA0). These interactions were calculated using the online software PoseView [38]. The green lines represent hydrophobic interactions and the black dotted lines represent hydrogen bonds.</p
Multicomponent reactions for the synthesis of bioactive compounds:A review
No full textMulticomponent reactions (MCRs) are composed of three or more reagents in which the final product has all or most of the carbon atoms from its starting materials. These reactions represent, in the medicinal chemistry context, great potential in the research for new bioactive compounds, since their products can present great structural complexity. The aim of this review is to present the main multicomponent reactions since the original report by Strecker in 1850 from nowadays, covering their evolution, highlighting their significance in the discovery of new bioactive compounds. The use of MCRs is, indeed, a growing field of interest in the synthesis of bioactive compounds and approved drugs, with several examples of commerciallyavailable drugs that are (or can be) obtained through these protocols.</p
Flow cytometry analyses.
No full text(A), the left panel presents the fluorescence histogram with the DNA profile of the cell-cycle phases (Sub-G1, G1, S and G2) of MDA-MB-231 cells in the presence of the control (DMSO 0.1%), colchicine and 10. The right panel shows the distribution of cells in different phases of the cell cycle for the control and after treatment with colchicine, 6, 7, 9 and 10 (B), the left panel displays the dot plot for the Annexin-V FITC/PI double stain of MDA-MB-231 cells for the control and after treatment with colchicine and 10. In the FITC- PI- quadrant are the alive cells, in the FITC+ quadrant are the apoptotic cells, and in the FITC+ PI+ and PI+ quadrants are the dead cells. The right panel shows the percentage of alive, apoptotic and dead cells of the control and after treatment with colchicine, 6, 7, 9 and 10. Statistical significance relative to control * P P P <0.001.</p
ChemInform Abstract: Highlights in the Solid-Phase Organic Synthesis of Natural Products and Analogues
No full textAntiprotozoal agents: How have they changed over a decade?
No full textNeglected tropical diseases are a diverse group of communicable diseases that are endemic in low- or low-to-middle-income countries located in tropical and subtropical zones. The number and availability of drugs for treating these diseases are low, the administration route is inconvenient in some cases, and most of them have safety, efficacy, or adverse/toxic reaction issues. The need for developing new drugs to deal with these issues is clear, but one of the most drastic consequences of this negligence is the lack of interest in the research and development of new therapeutic options among major pharmaceutical companies. Positive changes have been achieved over the last few years, although the overall situation remains alarming. After more than one decade since the original work reviewing antiprotozoal agents came to light, now it is time to question ourselves: How has the scenario for the treatment of protozoal diseases such as malaria, leishmaniasis, human African trypanosomiasis, and American trypanosomiasis changed? This review covers the last decade in terms of the drugs currently available for the treatment of these diseases as well as the clinical candidates being currently investigated.</p
Two series of new semisynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action
No full textAbstract
Background
The discovery and development of anti-malarial compounds of plant origin and semisynthetic derivatives thereof, such as quinine (QN) and chloroquine (CQ), has highlighted the importance of these compounds in the treatment of malaria. Ursolic acid analogues bearing an acetyl group at C-3 have demonstrated significant anti-malarial activity. With this in mind, two new series of betulinic acid (BA) and ursolic acid (UA) derivatives with ester groups at C-3 were synthesized in an attempt to improve anti-malarial activity, reduce cytotoxicity, and search for new targets. In vitro activity against CQ-sensitive Plasmodium falciparum 3D7 and an evaluation of cytotoxicity in a mammalian cell line (HEK293T) are reported. Furthermore, two possible mechanisms of action of anti-malarial compounds have been evaluated: effects on mitochondrial membrane potential (ΔΨm) and inhibition of β-haematin formation.
Results
Among the 18 derivatives synthesized, those having shorter side chains were most effective against CQ-sensitive P. falciparum 3D7, and were non-cytotoxic. These derivatives were three to five times more active than BA and UA. A DiOC6(3) ΔΨm assay showed that mitochondria are not involved in their mechanism of action. Inhibition of β-haematin formation by the active derivatives was weaker than with CQ. Compounds of the BA series were generally more active against P. falciparum 3D7 than those of the UA series.
Conclusions
Three new anti-malarial prototypes were obtained from natural sources through an easy and relatively inexpensive synthesis. They represent an alternative for new lead compounds for anti-malarial chemotherapy
