Doxorubicin-galactomannan nanoconjugates for potential cancer treatment.

In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.

4-Hydroxy-pyran-2-one and 3-hydroxy-N-methyl-2-oxindole derivatives of Salinispora arenicola from Brazilian marine sediments.

Three new 3-hydroxy-N-methyl-2-oxindole (1 and 2) and 4-hydroxy-pyran-2-one (3) derivatives, along with the known 3-hydroxy-N-methyl-2-oxindole (4) and 6-methoxy-N-methylisatin (5) were isolated from a marine Salinispora arenicola strain from sediments of the St. Peter and St. Paul Archipelago, Brazil. The structures of the new compounds were elucidated by a combination of spectroscopic (1D and 2D NMR and HR-ESIMS) data, including single-crystal X-ray diffraction analysis for 2 and 3. Compounds 1 to 5 were assayed for their antimicrobial properties, but only 4 and 5 were active against Enterococcus faecalis with MIC value of 15.6 µg/mL.

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.

In vivo growth inhibition of sarcoma 180 by latex proteins from Calotropis procera.

Latex of Calotropis procera has been described as a relevant source of pharmacologically active proteins, including proteins with anticancer activity. A previous in vitro study of laticifer proteins (LP) from C. procera reported that they had selective cytotoxic effects on human cancer cell lines. The aim of this study was to determine the effects of LP in vivo using mice transplanted with sarcoma 180. Biochemical, hematological, histopathological, and morphological analyses were performed in animals given LP by oral or intraperitoneal routes. LP significantly reduced tumor growth (51.83%) and augmented the survival time of animals for up to 4 days. Tumor growth inhibitory activity was lost when LP fraction was submitted to proteolysis, acidic treatment, or pretreated with iodoacetamide. However, LP retained its inhibitory activities on sarcoma 180 growth after heat treatment. Thus, it seems that heat-stable proteins are involved in tumor suppression. Biochemical parameters, such as the enzymatic activity of aspartate aminotransferase and alanine aminotransferase and urea content in serum were not affected in treated mice. It is worth noting that LP completely eliminated the 5-FU-induced depletion of leukocytes in mice even when given orally. The active proteins were recovered in a single fraction by ion exchange chromatography and still exhibited anticancer activity. This study confirms the pharmacological potential of proteins from the latex of C. procera to control sarcoma cell proliferation.

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.

Larvicidal and nematicidal activities of the leaf essential oil of Croton regelianus.

The chemical composition of the leaf essential oil of Croton regelianus collected from wild plants growing in two different sites at Ceará State (Brazil) was analyzed by GC/MS and GC-FID. Twenty monoterpenoids, representing more than 96% of the chemical composition of the oils, were identified and quantified. The oils showed similar chemical composition but considerable variation in the levels of each constituent. Ascaridole (33.9-17.0%), p-cymene (22.3-21.6%), and camphor (13.0-3.1%) were the predominant constituents. The monoterpene ascaridole was isolated and characterized by spectroscopic data. The essential oils and the isolated compounds were tested against Aedes aegypti and Artemia sp. larvae, and the root knot nematode Meloidogyne incognita. The bioassay results show that the essential oil of C. regelianus and ascaridole were moderately active against the M. incognita, but strongly effective against both A. aegypti and Artemia sp. larvae.