A5070572495- Bioactive Compounds and Antitumor Agents
- Cancer therapeutics and mechanisms
- Morinda citrifolia extract uses
- Synthesis and Biological Evaluation
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Research on Leishmaniasis Studies
- Synthesis and biological activity
- Synthesis of Organic Compounds
- Bioactive natural compounds
- Free Radicals and Antioxidants
- Natural product bioactivities and synthesis
- Chromatography in Natural Products
- Chronic Myeloid Leukemia Treatments
- Cancer Mechanisms and Therapy
- Parasitic Infections and Diagnostics
- Trypanosoma species research and implications
- Toxoplasma gondii Research Studies
- Traditional and Medicinal Uses of Annonaceae
- Immune Response and Inflammation
- Phytochemistry and biological activity of medicinal plants
- Bioactive Compounds in Plants
- Glioma Diagnosis and Treatment
- Ginger and Zingiberaceae research
- Cholinesterase and Neurodegenerative Diseases
Universidade Federal do Rio de Janeiro
2015-2025
Pontifical Catholic University of Rio de Janeiro
2016
The pterocarpanquinone LQB-118, previously demonstrated to be effective in vivo via oral delivery, was investigated for its mechanism selective parasite killing. Oxidative stress Leishmania amazonensis analysed by evaluating reactive oxygen species (ROS) production (2′,7′-dichlorodihydrofluorescein diacetate) and the loss of mitochondrial membrane potential (ΔΨm) using rhodamine, JC-1 MitoCapture. Ultrastructural analysis performed transmission electron microscopy (TEM). DNA fragmentation...
Phagocytosis is an important function of macrophages. However, when it's dysregulated, it could compromise homeostasis. Thus, this study aimed to assess the inhibitory activity pterocarpanquinone LQB 118 on murine macrophage phagocytosis. We used peritoneal macrophages isolated from mice evaluate impact (5 μM) modulation phagocytic and possible action mechanism related: IL-12 (by ELISA), NO Griess reaction),ROS production flow cytometry), intracellular signaling proteins (iNOS, P-Akt,...
Pterocarpanquinones 8a-c, previously synthesized in our laboratory, and an homologous series of derivatives, compounds 9a-c prepared this work, were evaluated on breast cancer cells (MCF-7) the parasites Leishmania amazonensis Plasmodium falciparum, culture. Compounds 8a-c more potent than tumor amazonensis. On other hand, showed to be active falciparum. All studied bioselective, presenting negligible cytotoxicity against fresh murine lymphocytes human activated by mitogen phytohemaglutinin (PHA).
Pterocarpanquinones (1a-e) and the aza-pterocarpanquinone (2) were synthesized through palladium catalyzed oxyarylation azaarylation of conjugate olefins, showed antineoplasic effect on leukemic cell lines (K562 HL-60) as well colon cancer (HCT-8), gliobastoma (SF-295) melanoma (MDA-MB435) lines. Some derivatives prepared (3-8) evaluated, allowing establishing structural requirements for activity in each series. Compound 1a best selectivity index special cells while 2 to be more bioselective...
A new pterocarpanquinone (5a) was synthesized through a palladium catalyzed oxyarylation reaction and transformed, electrophilic substitution reaction, into derivatives 5b-d. These compounds showed to be active against human leukemic cell lines lung cancer lines. Even multidrug resistant cells were sensitive 5a, which presented low toxicity toward peripheral blood mononuclear (PBMC) decreased the production of TNF-alpha by these cells. In laboratory pterocarpanquinones reduced sodium...
This paper describes the antileishmanial properties of LQB-118, a new compound designed by molecular hybridization, orally active in Leishmania amazonensis-infected BALB/c mice. In vitro activity was determined L. macrophages. For vivo studies, LQB-118 administered intralesionally (15 μg/kg/day, five times week), intraperitoneally (4.5 mg/kg/day, week) or to mice throughout experiments lasting 85 105 days. At end experiments, serum levels alanine aminotransferase, aspartate aminotransferase...
Visceral leishmaniasis (VL) is the most severe form of and second major cause death by parasites, after malaria. The arsenal drugs against small, each has a disadvantage in terms toxicity, efficacy, price, or treatment regimen. Our group focused on studying new drug candidates as alternatives to current treatments. pterocarpanquinone LQB-118 was designed synthesized based molecular hybridization, it exhibited antiprotozoal anti-leukemic cell line activities. previous work demonstrated that...
Dihydronaphthalenes were oxyarylated with <i>o</i>-iodophenols, in PEG-400 at 140 or 170 °C, leading regio- and stereoselectively to 5-carbapterocarpans. By using Pd(OAc)<sub>2</sub> (5–10 mol%) as precatalyst Ag<sub>2</sub>CO<sub>3</sub> (1.1 equiv) base (conditions A), products obtained good excellent chemical yields, 5–30 minutes, irrespective of the pattern substitution starting materials. Alternatively, when <i>p</i>-hydroxyacetophenone oxime derived palladacycle (1 was used...
Styrenes were coupled with 3-iodolawsone in PEG-400 at 90 °C, leading stereoselectively to (E)-stilbene-quinone hybrids through Heck reactions. The best reaction conditions found be the use of NaOH (3 equiv) and 10 mol% palladium acetate °C for 15 minutes. chemical yields reactions using styrenes electron-withdrawing groups (65–98%) greater than bearing electron-donating (7–32%) on aromatic ring. In particular, involving nitrostyrenes ones observed.
Pterocarpanquinone (+/-)-LQB-118 presents antineoplastic and antiparasitic properties also shows great inhibitory effect on TNF-α release in vitro. Here, its anti-inflammatory activity was evaluated a lipopolysaccharide (LPS)-induced lung inflammation model C57BL/6 mice. LPS inhalation induced marked neutrophil infiltration to the lungs which reduced by intraperitoneal treatment with similar manner that of dexamethasone even better than acetylsalicylic acid. Moreover, administration resulted...
Isoflavonoids constitute an important class of natural products, comprising great structural diversity. Known as phytoalexins and phytoestrogens, these compounds exhibit interesting biological activities. The corresponding carba-analogues, in which the oxygen atom at B-ring is replaced by a methylene, are emerging attractive alternative for preparation new bioactive compounds. In this review, we report our results on synthesis isoflavonoid analogues (5-carba-pterocarpans,...
Four new Cu/PPh3/naphtoquinone complexes were synthesized, characterized (IR, UV/visible, 1D/2D NMR, mass spectrometry, elemental analysis, and X-ray diffraction), evaluated as anticancer agents. We also investigated the reactive oxygen species (ROS) generation capacity of complex 4, considering well-established photochemical property naphthoquinones. Therefore, employing electron paramagnetic resonance (EPR) “spin trap”, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) technique, we identified...
We report the first synthesis of (±)-3,4-dihydroxy-8,9-methylenedioxypterocarpan, a natural isoflavonoid that shows antitumoral activity. The key step involved Heck reaction between 7,8-dibenzyloxychromen and organomercurial derived from sesamol, followed by debenzylation. adduct was also employed in corresponding coumestan derivative, using DDQ as oxidant agent.
Despite the development of new therapies for leishmaniasis, among 200 countries or territories reporting to WHO, 87 were identified as endemic Tegumentary Leishmaniasis and 75 Visceral Leishmaniasis. The identification antileishmanial drug candidates is essential fill discovery pipeline leishmaniasis. In hit molecule LQB-118 selected, first generation pterocarpanquinones was effective safe against experimental visceral cutaneous leishmaniasis via oral delivery. this paper, we report...
Abstract The electrochemistry of a redox‐based bioactive pterocarpanquinone, designated as LQB‐118, and its precursor chromenquinone (CQ) was investigated in protic aprotic media with focus on the reduction mechanism both media, reactivity oxygen, interaction biological targets, such DNA. UV/Vis spectroelectrochemistry clarified proposed mechanism. appearance bands at λ =331, 400, 600 nm suggests generation transient quinonemethides (QM). Electrochemical experiments revealed homogeneous...