10 research outputs found
Functional components of carob fruit: linking the chemical and biological space
The contribution of natural products to the drug-discovery pipeline has been remarkable since they have served as a rich source for drug development and discovery. Natural products have adapted, during the course of evolution, optimum chemical scaffolds against a wide variety of diseases, including cancer and diabetes. Advances in high-throughput screening assays, assisted by the continuous development on the instrumentation’s capabilities and omics, have resulted in charting a large chemical and biological space of drug-like compounds, originating from natural sources. Herein, we attempt to integrate the information on the chemical composition and the associated biological impact of carob fruit in regards to human health. The beneficial and health-promoting effects of carob along with the clinical trials and the drug formulations derived from carob’s natural components are presented in this review
Lipophilic ester and amide derivatives of rosmarinic acid protect cells against H2O2-induced DNA damage and apoptosis: The potential role of intracellular accumulation and labile iron chelation
Phenolic acids represent abundant components contained in human diet. However, the negative charge in their carboxylic group limits their capacity to diffuse through biological membranes, thus hindering their access to cell interior. In order to promote the diffusion of rosmarinic acid through biological membranes, we synthesized several lipophilic ester- and amide-derivatives of this compound and evaluated their capacity to prevent H2O2-induced DNA damage and apoptosis in cultured human cells. Esterification of the carboxylic moiety with lipophilic groups strongly enhanced the capacity of rosmarinic acid to protect cells. On the other hand, the amide-derivatives were somewhat less effective but exerted less cytotoxicity at high concentrations. Cell uptake experiments, using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), illustrated different levels of intracellular accumulation among the ester- and amide-derivatives, with the first being more effectively accumulated, probably due to their extensive hydrolysis inside the cells. In conclusion, these results highlight the hitherto unrecognized fundamental importance of derivatization of diet-derived phenolic acids to unveil their biological potential
Lipophilic ester and amide derivatives of rosmarinic acid protect cells against H2O2-induced DNA damage and apoptosis: The potential role of intracellular accumulation and labile iron chelation
Phenolic acids represent abundant components contained in human diet. However, the negative charge in their carboxylic group limits their capacity to diffuse through biological membranes, thus hindering their access to cell interior. In order to promote the diffusion of rosmarinic acid through biological membranes, we synthesized several lipophilic ester- and amide-derivatives of this compound and evaluated their capacity to prevent H2O2-induced DNA damage and apoptosis in cultured human cells. Esterification of the carboxylic moiety with lipophilic groups strongly enhanced the capacity of rosmarinic acid to protect cells. On the other hand, the amide-derivatives were somewhat less effective but exerted less cytotoxicity at high concentrations. Cell uptake experiments, using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), illustrated different levels of intracellular accumulation among the ester- and amide-derivatives, with the first being more effectively accumulated, probably due to their extensive hydrolysis inside the cells. In conclusion, these results highlight the hitherto unrecognized fundamental importance of derivatization of diet-derived phenolic acids to unveil their biological potential
Unveiling the interaction profile of rosmarinicacid and its bioactive substructures with serumalbumin
Rosmarinic acid, a phytochemical compound, bears diverse pharmaceutical profile. It is composed by two
building blocks: caffeic acid and a salvianic acid unit. The interaction profile, responsible for the delivery
of rosmarinic acid and its two substructure components by serum albumin remains unexplored. To unveil
this, we established a novel low-cost and efficient method to produce salvianic acid from the parent compound. To probe the interaction profile of rosmarinic acid and its two substructure constituents with the
different serum albumin binding sites we utilised fluorescence spectroscopy and competitive saturation
transfer difference NMR experiments. These studies were complemented with transfer NOESY NMR experiments. The thermodynamics of the binding profile of rosmarinic acid and its substructures were addressed
using isothermal titration calorimetry. In silico docking studies, driven by the experimental data, have
been used to deliver further atomic details on the binding mode of rosmarinic acid and its structural component
Unveiling the interaction profile of rosmarinic acid and its bioactive substructures with serum albumin
Rosmarinic acid, a phytochemical compound, bears diverse pharmaceutical profile. It is composed by two building blocks: caffeic acid and a salvianic acid unit. The interaction profile, responsible for the delivery of rosmarinic acid and its two substructure components by serum albumin remains unexplored. To unveil this, we established a novel low-cost and efficient method to produce salvianic acid from the parent compound. To probe the interaction profile of rosmarinic acid and its two substructure constituents with the different serum albumin binding sites we utilised fluorescence spectroscopy and competitive saturation transfer difference NMR experiments. These studies were complemented with transfer NOESY NMR experiments. The thermodynamics of the binding profile of rosmarinic acid and its substructures were addressed using isothermal titration calorimetry. In silico docking studies, driven by the experimental data, have been used to deliver further atomic details on the binding mode of rosmarinic acid and its structural components
. Inclusion of Quercetin in Gold Nanoparticles Decorated with Supramolecular Hosts Amplifies Its Tumor Targeting Properties
Despite the anticancer potential of natural products (NPs), their limited bioavailability necessitates
laborious derivatization or covalent conjugation to delivery vehicles. To unleash their potential we
developed a nanohybrid delivery platform with noncovalently tunable surface. Initially, the active
compound was encapsulated in a macrocycle, p-sulphonatocalix[4]arene, enabling a 62,000-fold
aqueous solubility amplification as also a 2.9-fold enhancement in its cytotoxicity with respect to
the parent compound in SW-620 colon cancer cells. A pH stimuli responsive behavior was
recorded for this formulate, where a programmable release of quercetin from the macrocycle was
monitored in acidic environment. Then, a nanoparticle gold core was decorated with calixarene
hosts to accommodate non-covalently NPs. The loaded nanocarrier with the NP quercetin
dramatically enhanced the cytotoxicity (>50 fold) of the parent NP in colon cancer and altered its
cell membrane transport mode. In vivo experiments in a mouse 4T1 tumor model showed a
reduction of tumor volume in mice treated with quercetin-loaded nanoparticles without apparent
toxic effects. Further analysis of the tumor-derived RNA highlighted that treatment with quercetinloaded nanoparticles altered the expression of 27 genes related to apoptosis
Direct Binding of Bcl‑2 Family Proteins by Quercetin Triggers Its Pro-Apoptotic Activity
Bcl-2 family proteins are important
regulators of apoptosis and
its antiapoptotic members, which are overexpressed in many types of
cancer, are of high prognostic significance, establishing them as
attractive therapeutic targets. Quercetin, a natural flavonoid, has
drawn much attention because it exerts anticancer effects, while sparing
normal cells. A multidisciplinary approach has been employed herein,
in an effort to reveal its mode of action including dose–response
antiproliferative activity and induced apoptosis effect, biochemical
and physicochemical assays, and computational calculations. It may
be concluded that, quercetin binds directly to the BH3 domain of Bcl-2
and Bcl-xL proteins, thereby inhibiting their activity and promoting
cancer cell apoptosis