Publications by authors named "Rodrigo B Andrade"

Neonates have an immature immune system, which increases their vulnerability to infectious agents and inflammatory insults. The administration of the immunostimulatory agent lipopolysaccharide (LPS) has been shown to induce the expression of pro-inflammatory cytokines and cause behavior alterations in rodents at different ages. However, the effects of LPS administration during the neonatal period and its consequences during immune system maturation remain to be elucidated.

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The iboga alkaloids are promising antiaddictive and neuroregeneration candidates for medical treatment. There is a lack of studies for C20-epi iboga alkaloids due to the synthetic difficulties. Herein we report the shortest total synthesis of (+)-epiibogamine in seven steps from trimethyl orthobutyrate.

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The diastereoselective α-hydroxylation of --butanesulfinyl metallodienenamine and metalloenamines with Davis oxaziridine affords α-hydroxy -sulfinyl imines with 50-88% yield and up to 98:2 diastereomeric ratio. Dramatic changes in diastereoselectivity and stereoselectivity were observed by choice of metal bases. The mechanistic understanding for the switch in diastereoselectivity was assisted by DFT computational modeling, which suggests the facial approach is governed by aza-enolate geometry.

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Enzymatic biotransformation has become a widely used technique in synthetic chemistry to achieve difficult chemical transformations. Cytochrome P450 monooxygenase enzymes found in nature carry out a wide range of difficult chemical reactions, such as the oxidation of the monoterpene indole alkaloid (-)-tabersonine at the unreactive 16th position on the indoline benzene ring in the biosynthesis of biologically active natural products such as the bis-indole alkaloid (-)-melodinine K. Herein, we describe the first semisynthesis of (-)-melodinine K enabled by a biological gram scale route to the northern fragment, (-)-16-hydroxytabersonine, as well as a chemical route to the southern fragment, (-)-pachysiphine, both derived from (-)-tabersonine and subsequently coupled in only eight linear steps.

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We demonstrated here a series of terpenoid alkaloids can be quickly prepared using semisynthesis from naturally sourced tabersonine, featuring multiple oxygen-based substituents on the indole ring such as hydroxy and methoxy groups. This panel of complex compounds enabled the exploration of indole modifications to optimize the indole alkaloids' anticancer activity, generating lead compounds (, with C15-hydroxy, C16-methoxy, and/or C17-methoxy derivatizations) that potently inhibit cancer cell line growth in the single-digit micromolar range. These results can help guide the development of terpenoid alkaloid therapeutics.

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The marked rise in bacterial drug resistance has created an urgent need for novel antibacterials belonging to new drug classes and ideally possessing new mechanisms of action. The superior biological activity of solithromycin against streptococci and other bacteria causative of community-acquired pneumonia pathogens, compared to telithromycin and other macrolides encouraged us to extensively explore this class of antibiotics. We, thus, present the design and synthesis of a novel series of solithromycin analogs.

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Of Nature's nearly 3000 unique monoterpene indole alkaloids derived from tryptophan, those members belonging to the Aspidosperma and Strychnos families continue to impact the fields of natural products (i.e., isolation, structure determination, biosynthesis) and organic chemistry (i.

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The domino Michael/Mannich (DMM) annulation reaction between an -sulfinyl lithiodienamine and an electrophilic alkene is developed for the synthesis of chiral 2-amino cyclohexenes, a key building block in asymmetric synthesis. The DMM reaction proceeds at low temperature while maintaining the stereochemical fidelity. The product functionalized amino cyclohexenes, here obtained in 55-82% yield with diastereomeric ratios as high as >19:1.

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There is an urgent need for new antibiotics to mitigate the existential threat posed by antibiotic resistance. Within the ketolide class, solithromycin has emerged as one of the most promising candidates for further development. Crystallographic studies of bacterial ribosomes and ribosomal subunits complexed with solithromycin have shed light on the nature of molecular interactions (π-stacking and H-bonding) between from the biaryl side-chain of the drug and key residues in the 50S ribosomal subunit.

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Small molecule target identification is a critical step in modern antibacterial drug discovery, particularly against multi-drug resistant pathogens. Albocycline (ALB) is a macrolactone natural product with potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) whose mechanism of action has been elusive to date.

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Albocycline (ALB) is a unique macrolactone natural product with potent, narrow-spectrum activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate (VISA), and vancomycin-resistant S. aureus (VRSA) strains (MIC = 0.5-1.

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Efficiency is a key organizing principle in modern natural product synthesis. Practical criteria include time, cost, and effort expended to synthesize the target, which tracks with step-count and scale. The execution of a natural product synthesis, that is, the sum and identity of each reaction employed therein, falls along a continuum of chemical (abiotic) synthesis on one extreme, followed by the hybrid chemoenzymatic approach, and ultimately biological (biosynthesis) on the other, acknowledging the belongs to Nature.

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Herein, we report the first asymmetric total synthesis of aspidospermatan indole alkaloid (+)--condyfoline () in 15 steps from commercially available 2-methylindole-3-carboxaldehyde. Key steps include (1) our domino Michael/Mannich annulation method of -sulfinyl metallodienamines to set three contiguous stereocenters, (2) LiHMDS-mediated cyclization of an ω-tosyloxy -sulfinamide to prepare the signature indole-fused 2-azabicyclo[3.3.

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Objective: To evaluate the effects of the carmine cochineal-resistant spineless cactus genotypes cv. Orelha de Elefante Mexicana (Opuntia) and Miúda (Nopalea) on the intake and digestibility of nutrients, ingestive behavior, performance, and ultrasound measurements of growing lambs.

Methods: Thirty-six male (non-castrated) Santa Inês lambs were used, with an average age of 6 months and an initial average weight of 22.

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Novel antibacterial drugs that treat multidrug resistant pathogens are in high demand. We have synthesized analogs of solithromycin using Cu(I)-mediated click chemistry. Evaluation of the analogs using Minimum Inhibitory Concentration (MIC) assays against resistant Staphylococcus aureus, Escherichia coli, and multidrug resistant pathogens Enterococcus faecium and Acinetobacter baumannii showed they possess potencies similar to those of solithromycin, thus demonstrating their potential as future therapeutics to combat the existential threat of multidrug resistant pathogens.

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Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays.

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click chemistry has been a powerful method for fragment-based drug design since its discovery in 2002. Recently, we demonstrated that the bacterial ribosome can template the azide-alkyne cycloaddition reaction to expedite the discovery of novel antibiotics. We now report this process can be performed in an antibiotic-resistant bacterial cell.

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Lochnericine is a major monoterpene indole alkaloid (MIA) in the roots of Madagascar periwinkle (). Lochnericine is derived from the stereoselective C6,C7-epoxidation of tabersonine and can be metabolized further to generate other complex MIAs. While the enzymes responsible for its downstream modifications have been characterized, those involved in lochnericine biosynthesis remain unknown.

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Strychnogucine B is a bisindole alkaloid previously isolated from that possesses promising antiplasmodial properties. This compound was synthesized in four steps from (-)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its antimalarial activity was determined intraperitoneally at 30 mg/kg/d in a murine model.

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Antibiotic resistance is a serious threat to global public health, and methicillin-resistant Staphylococcus aureus (MRSA) is a poignant example. The macrolactone natural product albocycline, derived from various Streptomyces strains, was recently identified as a promising antibiotic candidate for the treatment of both MRSA and vancomycin-resistant S. aureus (VRSA), which is another clinically relevant and antibiotic resistant strain.

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Article Synopsis
  • * MAT was found to be ineffective in yeast and plants, prompting researchers to identify other potential acetyltransferase candidates that correlate with T19H expression, ultimately discovering TAT, which acetylates root-specific MIAs more efficiently than MAT.
  • * TAT’s role in the biosynthetic pathway and its successful heterologous expression in plants allows for more efficient metabolic engineering of MIAs, enabling the creation of customized MIAs that combine
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β-Alanine occurs naturally in the human central nervous system and performs different functions. It can act as either a neurotransmitter or a neuromodulator, depletion of taurine levels and competitive antagonist of γ-aminobutyric acid (GABA). The β-amino acid accumulation exerts an important biological function as delay in brain development, oxidative stress and disturbances in energy metabolism, characterized as an inborn error of metabolism classified as β-alaninemia.

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Hypoxanthine is the major purine involved in the salvage pathway of purines in the brain. High levels of hypoxanthine are characteristic of Lesch-Nyhan Disease. Since hypoxanthine is a purine closely related to ATP formation, the aim of this study was to investigate the effect of intrastriatal hypoxanthine administration on neuroenergetic parameters (pyruvate kinase, succinate dehydrogenase, complex II, cytochrome c oxidase, and ATP levels) and mitochondrial function (mitochondrial mass and membrane potential) in striatum of rats.

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Although many studies show the toxic effects of proline, recently it has been reported some anti-inflammatory effect of this amino acid. Our principal objective was to investigate the effects of proline on the alterations caused by LPS (lipopolysaccharide) administration in the cerebral cortex and cerebellum of young Wistar rats. The animals were divided into four groups: control (0.

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