Bruna S. Goldani

Organocatalytic synthesis and evaluation of 7-chloroquinoline-1,2,3-triazoyl carboxamides as potential antinociceptive, anti-inflammatory and anticonvulsant agent

We describe herein our results on the organocatalytic synthesis and pharmacological properties of 7-chloroquinoline-1,2,3-triazoyl carboxamides. This class of compounds was synthesized in good to excellent yields by the reaction of 4-azido-7-chloroquinoline with a range of β-oxo-amides in the presence of a catalytic amount of pyrrolidine (5 mol%). The obtained compound 3a was screened for anticonvulsant, antinociceptive and anti-inflammatory activities in vivo. The results demonstrated that compound 3a was effective in decreasing the appearance of seizures induced by pilocarpine and pentylenetetrazole. In addition, compound 3a demonstrated antinoceptive and anti-inflammatory properties for combating acute pain. This protocol is an efficient method for the production of new heterocyclic compounds with pharmacological activities.

Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans

Abstract Organic selenium and tellurium compounds are known for their broad‐spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high‐throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C. elegans) as a model for the assessment of pharmacological and toxicological parameters following exposure to two 4‐phenylchalcogenil‐7‐chloroquinolines derivatives (PSQ for selenium and PTQ for tellurium‐containing compounds). While non‐lethal concentrations (NLC) of PTQ and PSQ attenuated paraquat‐induced effects on survival, lifespan and oxidative stress parameters, lethal concentrations (LC) of PTQ and PSQ alone are able to impair these parameters in C. elegans. We also demonstrate that DAF‐16/FOXO and SKN‐1/Nrf2 transcription factors underlie the mechanism of action of these compounds, as their targets sod‐3, gst‐4 and gcs‐1 were modulated following exposures in a daf‐16‐ and skn‐1‐dependent manner. Finally, in accordance with a disturbed thiol metabolism in both LC and NLC, we found higher sensitivity of trxr‐1 worm mutants (lacking the selenoprotein thioredoxin reductase 1) when exposed to PSQ. Finally, our study suggests new targets for the investigation of organochalcogen pharmacological effects, reinforcing the use of C. elegans as a powerful platform for preclinical approaches. Graphical abstract Figure. No caption available. HighlightsPSQ and PTQ at LC induce oxidative damage and impair C. elegans physiology.PSQ and PTQ at NLC protect C. elegans from oxidative stress induced by PQ.daf‐16/FOXO and skn‐1/NRF2 modulations are involved in PSQ and PTQ effects.sod‐3, gcs‐1, gst‐4, and trxr‐1 expression are altered after PSQ and PTQ exposure.

Sonochemistry in organocatalytic enamine-azide [3+2] cycloadditions: A rapid alternative for the synthesis of 1,2,3-triazoyl carboxamides

We described herein the use of sonochemistry in the organocatalytic enamine-azide [3+2] cycloadditions of β-oxo-amides with a range of substituted aryl azides. These sonochemical promoted reactions were found to be amenable to a range of β-oxo amides or aryl azides, providing an efficient access to new N-aryl-1,2,3-triazoyl carboxamides in good to excellent yields and short times of reaction.

Synthesis of symmetrical and unsymmetrical tellurides via silver catalysis

We describe here a simple and efficient methodology for the cross-coupling reaction of diaryl ditellurides with aryl boronic acids catalyzed by AgNO3. The general applicability and wide substrate scope make this an interesting method for the synthesis of a series of symmetrical and unsymmetrical diaryl tellurides. This silver-catalyzed protocol tolerates a variety of diaryl ditellurides as well as aryl boronic acids by using only 10 mol% of AgNO3 to provide the desired products in high yields. The reaction mechanism was proposed after high resolution mass spectrometry analysis and the active (PhTe)2AgIII intermediate could be detected.

Copper Catalysis and Organocatalysis Showing the Way: Synthesis of Selenium-Containing Highly Functionalized 1,2,3-Triazoles

This article provides a comprehensive overview of reported methods - particularly copper- and organocatalyzed reactions - for the regioselective syntheses of selenium-containing 1,2,3-triazoles systems. These chemical entities are prevalent cores in biologically active compounds and functional materials. In view of their unique properties, substantial efforts have been paid for the design and development of practical approaches for the synthesis of these scaffolds.

Apoptosis induction by 7-chloroquinoline-1,2,3-triazoyl carboxamides in triple negative breast cancer cells

Breast cancer is a major public health burden in both developed and developing countries and there is still a need to screen new molecules with different modes of actions. The aims of this study were to evaluate the selectivity profile, apoptotic cell death and cell cycle arrest induced by 7-chloroquinoline-1,2,3-triazoyl carboxamides derivatives in hormonal-dependent and hormonal-independent breast cancer cells. Results showed significantly decreased MCF-7 and MDA-MB-231 cells viability in vitro in a dose dependent manner after treatment with 7-chloroquinoline derivatives QTCA-1, QTCA-2 and QTCA-3. QTCA-1 displayed the highest cytotoxic activity from all the tested compounds in MDA-MB-231 with IC50 values of 20.60, 20.42 and 19.91μM in 24, 48 and 72h of treatment respectively. Apoptosis induction was also significantly higher in the hormonal-independent breast cancer cells, with 80.4% of dead cells in MDA-MB-231 and only 16.8% of dead in MCF-7 cells. As a result, G0/G1 cycle arrest was observed in MCF-7 cells and no cell cycle arrest at all was observed in MDA-MB-231 cells. Molecular docking showed a high affinity of QTCA-1 to PARP-1, Scr and PI3K/mTOR targets. These results suggest a strong activity of the 7-chloroquinoline derivative QTCA-1 in independent-hormonal cells and suggest selectivity for triple negative cells.