Dual responsive dextran-graft-poly (N-isopropylacrylamide)/doxorubicin prodrug via Schiff base reaction.

Stimulus-responsive nanoparticles stand out in studies for cancer treatment since these systems can promote a selective release of the drug in tumor tissues and cells, minimizing the effects caused by conventional chemotherapy. Dextran-graft-poly (N-isopropylacrylamide) copolymers were synthesized via Schiff base formation. The synthesis of copolymers was confirmed by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (NMR) and the analyses of dynamic light scattering (DLS) showed that the copolymers were thermal and pH dual-responsive. The chemotherapy drug doxorubicin (DOX) was conjugated to the copolymers via Schiff base formation, obtaining nanoparticles by self-assembling with size smaller than 130 nm. A higher percentage of doxorubicin was released at pH 5.0 (59.1 ± 2.1%) compared to physiological pH (34.9 ± 4.8%), confirming a pH-sensitive release profile. The in vitro cytotoxicity assay demonstrated that DOX-loaded nanoparticles can inhibit cancer cell proliferation and promote reduced cytotoxicity in non-tumor cells. The D45kP30k-DOX nanoparticles induced morphological changes in HCT-116 cells suggesting cell death and the cell uptake assay indicated that the nanoparticles can be internalized by endocytosis. Therefore, DOX-loaded nanoparticles exhibited potential as smart systems for cancer treatment.

Poly(ε-caprolactone) grafted cashew gum nanoparticles as an epirubicin delivery system.

Polysaccharide based copolymers have been the focus of several research, particularly for the development of drug delivery systems. This study reports on the preparation of nanoparticles from an amphiphilic copolymer obtained by the poly(ε-caprolactone) graft in the structure of cashew gum, via ring-opening polymerization. The synthesis of copolymers was confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. The copolymers exhibit self-organization capability in water, with critical association concentration of 42 and 50 µg mL-1. The nanoparticle hydrodynamic diameters (212 and 202 nm) revealed a decreasing trend with increasing poly(ε-caprolactone) graft percentage. Epirubicin was used as an anticancer drug model and incorporated into the nanoparticles. The encapsulation efficiency reached 50% and 5.0% drug load. Nanoparticles showed an epirubicin controlled release profile, with maximum release of 93.0 ± 4.0% in 72 h, as well as excellent biocompatibility, according to hemolysis and cytotoxicity assays.

Terpene Esters from Natural Products: Synthesis and Evaluation of Cytotoxic Activity

ABSTRACT Natural steroids and triterpenes such as b-sitosterol, stigmasterol, lupeol, ursolic and betulinic acids were transformed into its hexanoic and oleic esters, to evaluate the influence of chemical modification towards the cytotoxic activities against tumor cells. The derivatives were evaluated against five tumor cell lines [OVCAR-8 (ovarian carcinoma); SF-295 (glioblastoma); HCT-116 (colon adenocarcinoma); HL-60 (leukemia); and PC-3 (prostate carcinoma)] and the results showed only betulinic acid hexyl ester exhibits cytotoxic potential activity.

Terpene Esters from Natural Products: Synthesis and Evaluation of Cytotoxic Activity.

Natural steroids and triterpenes such as b-sitosterol, stigmasterol, lupeol, ursolic and betulinic acids were transformed into its hexanoic and oleic esters, to evaluate the influence of chemical modification towards the cytotoxic activities against tumor cells. The derivatives were evaluated against five tumor cell lines [OVCAR-8 (ovarian carcinoma); SF-295 (glioblastoma); HCT-116 (colon adenocarcinoma); HL-60 (leukemia); and PC-3 (prostate carcinoma)] and the results showed only betulinic acid hexyl ester exhibits cytotoxic potential activity.

Perezone, from the gorgonian Pseudopterogorgia rigida, induces oxidative stress in human leukemia cells

Abstract Four bisabolanes 1–4, including perezone (1) and triacetyl perezone (2), were isolated through a bioassay-guided fractionation of the extract obtained from the Caribbean gorgonian coral Pseudopterogorgia rigida collected during an expedition cruise to the Bahamas. All isolated compounds showed to be cytotoxic toward panel of four human tumor cell lines, as quantified by the MTT assay after 72 h incubation. Perezone (1), the most active one, was further analyzed, showing to be cytotoxic, but not selective, in a 12-cell line panel comprising tumor and non-tumor, as well as human and murine cells. Additionally, 1 was assayed for cytotoxicity against HL-60 leukemic cells. Pre-treatment with an acute free radical scavenger (L-NAC) before exposure of cells to perezone virtually eliminated the generation of intracellular ROS and lessened its severe cytotoxicity. The protective effect delivered by L-NAC evidences that the mechanism of perezone-induced cytotoxicity is partially associated to production of ROS and a consequent induction of oxidative stress.

Antifungal ether diglycosides from Matayba guianensis Aublet.

Since the 1960s, fungal infections have become a major worldwide public health problem. Antifungal treatments have many limitations, such as toxicity and resistance. Matayba guianensis Aublet (Sapindaceae) was chemically investigated as part of our ongoing search for lead molecules against fungi in the Brazilian Cerrado biome. The ethanolic extract of M. guianensis root bark revealed the presence of two previously unreported ether diglycosides: matayoside E (1) and F (2) with anti Candida activity, along with two known compounds: cupanioside (3) and stigmasterol (4).

Novel platinum(II) complexes of 3-(aminomethyl)naphthoquinone Mannich bases: synthesis, crystal structure and cytotoxic activities.

The first examples of platinum(II) complexes of 3-(aminomethyl)naphthoquinone Mannich bases have been synthesised and their crystal structures are described. Neutral and charged complexes have been obtained, fully characterised and their cytotoxic activities have also been investigated. 3-[(R(1)-amino)(pyridin-2-yl)methyl]-2-hydroxy-1,4-naphthoquinones (R(1) = n-Bu, HL1; Bn, HL2; furfuryl, HL3; n-heptyl, HL4 and n-decyl, HL5) coordinate to platinum(II) through the two nitrogen atoms. The neutral complexes cis-[Pt(HL)Cl(2)] 1a-5a are analogous to cisplatin with the bidentate ligand HL and two chlorine atoms occupying cis positions. In the charged complexes cis-[Pt(L(-))(NH(3))(2)]NO(3)1b-5b the deprotonated form of the ligand L(-) also coordinates via the nitrogen atoms, and the other two positions around the platinum(II) ion are completed with NH(3) ligands. The cytotoxic activities of all compounds have been tested for six different cancer cell lines: MDA-MB-435 (melanoma), HL-60 (promyelocytic leukaemia), HCT-8 (colon), SF-295 (brain), OVCAR-8 (ovary) and PC-3 (prostate). Proligands HL4 and HL5 have exhibited high activity against HL-60 (IC(50) = 1.9 and 3.8 µmol L(-1), respectively), HCT-8 (IC(50) = 1.6 and 1.7 µmol L(-1), respectively) and SF-295 (IC(50) = 1.1 and 1.7 µmol L(-1), respectively). The chlorido complexes 1a-5a have shown high to moderate cytotoxic activities, complex 4a (R(1) = n-heptyl) being more active than proligand HL4 against melanoma (IC(50) = 6.4 and > 40 µmol L(-1), respectively) and more active than cisplatin against all tested cell lines. Among the amine charged complexes only 4b and 5b have exhibited significant cytotoxic activity against the tested cell lines, although they were only moderately active against the PC-3 cell line (IC(50) = 29.9 and 15.6 µmol L(-1), respectively). In general the compounds with the longest carbon chains (R(1) = n-heptyl and n-decyl) have exhibited the highest activities.

Oxidative stress induction by (+)-cordiaquinone J triggers both mitochondria-dependent apoptosis and necrosis in leukemia cells.

(+)-Cordiaquinone J is a 1,4-naphthoquinone isolated from the roots of Cordia leucocephala that has antifungal and larvicidal effects. However, the cytotoxic effects of (+)-cordiaquinone J have never being explored. In the present study, the effect of (+)-cordiaquinone J on tumor cells viability was investigated, showing IC(50) values in the range of 2.7-6.6muM in HL-60 and SF-295 cells, respectively. Studies performed in HL-60 leukemia cells indicated that (+)-cordiaquinone J (1.5 and 3.0muM) reduces cell viability and 5-bromo-2-deoxyuridine incorporation after 24h of incubation. (+)-Cordiaquinone J showed rapid induction of apoptosis, as indicated by phosphatidylserine externalization, caspase activation, DNA fragmentation, morphologic changes, and rapid induction of necrosis, as indicated by the loss of membrane integrity and morphologic changes. (+)-Cordiaquinone J altered the redox potential of cells by inducing the depletion of reduced GSH intracellular content, the generation of reactive oxygen species and the loss of mitochondrial membrane potential. However, pre-treatment of cells with N-acetyl-l-cysteine abolished most of the observed effects related to (+)-cordiaquinone J treatment, including those involving apoptosis and necrosis induction.

Prevención de lesiones y retorno seguro al trabajo para pacientes con problemas lumbares que acuden al servicio de fisioterapia en la policlínica Presidente Remón / Prevention of lesions and the secure return of patients with lumbar problems that seek the physical therapy services of the presidente Remón policlinic to their work

Se propone conocer el manejo más apropiado de los pacientes con diagnóstico de lesiones lumbares en el ámbito internacional, obtener datos sobre el particular a nivel nacional que permite conocer las diferencias para mejorarlas y proporcionar las conclusiones y recomendaciones que ayuden a divulgar los conocimientos sobre el problema

Prevención de lesiones y retorno seguro al trabajo para pacientes con problemas lumbares que acuden al servicio de fisioterapia de la Policlínica Presidente Remón / Prevention of lesions and the secure return of patients with lumbar problems that sec the physical therapy services of the president Remon Policlinic to their work

Tiene como objetivo conocer el manejo más apropiado de los pacientes con diagnóstico de lesiones lumbares en el ámbito internacional, obtener datos sobre el particular a nivel nacional que permite conocer las diferencias para mejorarlas y proporcionar las conclusiones y recomendaciones que permitan divulgar los conocimientos sobre el problema