Luana da S. M. Forezi

Synthesis of new porphyrin/4-quinolone conjugates and evaluation of their efficiency in the photoinactivation of Staphylococcus aureus

Simple methodologies giving access to a new series of pophyrin/4-quinolone conjugates 6 and to the corresponding intra-cyclized derivatives 8 are described. The key steps to obtain 6 involved palladium-catalyzed amination reactions of 6-bromo-4-quinolones containing N-ethyl, N-pentyl and N-ribofuransyl substituents with (2-amino-5,10,15,20-tetraphenylporphyrinato)nickel(II) followed by demetallation. Compounds 8 were obtained from compounds 4, the nickel(II) complexes of 6, by an oxidative intracylization approach. The new conjugates were fully characterized and the evaluation of singlet oxygen production showed that these compounds possess good to high capability to generate singlet oxygen. The efficacy of these derivatives to photoinactivate Staphylococcus aureus, a Gram-positive bacteria, was evaluated and the best results were obtained with the N-ethyl derivatives 8a and 6a.

1,2,3-Triazolyl-4-oxoquinolines: A feasible beginning for promising chemical structures to inhibit oseltamivir-resistant influenza A and B viruses

We described the synthesis of a new congener series of 1,2,3-triazolyl-4-oxoquinolines and evaluated their ability to inhibit oseltamivir (OST)-resistant influenza strains. Oxoquinoline derivative 1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity. Compound 1i inhibited influenza virus replication with an EC50 of 0.2μM with less cytotoxicity than OST, and also inhibited different OST-resistant NAs. These results suggest that 1,2,3-triazolyl-4-oxoquinolines represent promising lead molecules for further anti-influenza drug design.

Synthesis, cytotoxicity and mechanistic evaluation of 4-oxoquinoline-3-carboxamide derivatives: finding new potential anticancer drugs.

As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10–18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.

Carbene Transfer Reactions Catalysed by Dyes of the Metalloporphyrin Group

Carbene transfer reactions are very important transformations in organic synthesis, allowing the generation of structurally challenging products by catalysed cyclopropanation, cyclopropenation, carbene C-H, N-H, O-H, S-H, and Si-H insertion, and olefination of carbonyl compounds. In particular, chiral and achiral metalloporphyrins have been successfully explored as biomimetic catalysts for these carbene transfer reactions under both homogeneous and heterogeneous conditions. In this work the use of synthetic metalloporphyrins (MPorph, M = Fe, Ru, Os, Co, Rh, Ir, Sn) as homogeneous or heterogeneous catalysts for carbene transfer reactions in the last years is reviewed, almost exclusively focused on the literature since the year 2010, except when reference to older publications was deemed to be crucial.

Synthesis and Antifungal Activity of Coumarins Derivatives Against Sporothrix spp.

Sporotrichosis is a serious public health problem in Brazil that affects human patients and domestic animals, mainly cats. Thus, the search for new antifungal agents is required also due to the emergence and to the lack of effective drugs available in the therapeutic arsenal. The aim of this study was to evaluate the in vitro antifungal profile of two synthetic series of coumarin derivatives against Sporothrix schenckii and Sporothrix brasiliensis. The three-components synthetic routes used for the preparation of coumarin derivatives have proved to be quite efficient and compounds 16 and 17 have been prepared in good yields. The inhibitory activity of nineteen synthetic coumarins derivatives 16a-i and 17a-j were evaluated against Sporothrix spp. yeasts and the most potent compounds were 16b and 17i. However, according to concentrations able to inhibit (minimum inhibitory concentrations) and kill (minimum fungicidal concentrations) the cells, 17i was more effective than 16b against Sporothrix spp. Thus, 17i exhibited good antifungal activity against S. brasiliensis and S. schenckii, suggesting that it is an important scaffold for the development of novel antifungal agents.

Alternative Routes to the Click Method for the Synthesis of 1,2,3-Triazoles

Heterocyclic rings having nitrogen atoms are the molecular fragments most used in drug design by using the tools of medicinal chemistry. The 1,2,4-triazole rings are part of an extensive family of drugs that are in use in the pharmaceutical market. More recently, 1,2,3-triazole rings have begun to arouse the great interest of scientists and therefore, many researches have been developed seeking the synthesis of new substances and their possible biological activities. A number of articles have been published by us and others highlighting the synthetic and biological aspects of 1,2,3-triazoles. The growth of new substances of this class was largely due to the simple and selective synthetic method of 1,2,3- triazole ring developed by Sharpless et al. However, some 1,2,3-triazole cannot be synthesized by this method. This review focuses on other synthetic methods that give access to other variations around the 1,2,3-triazole core. The systematic arrangement in this review explores the possibility of providing practical guidance to alternatives of this heterocycle. It has been divided into sections according to the types of starting materials and reactions.

Synthesis and Biological Evaluation of the Coumarins Derivatives as Potential Inhibitors of the Production of the Pseudomonas aeruginosa Virulence Factor Pyocyanin

Antimicrobial Resistance (AMR) is a serious problem for the humans since it threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. One way around this problem is to act on the virulence factors, produced by bacteria, which increase their infection effectiveness. In view of these facts, new coumarin derivatives were synthesized and evaluated for their anti-virulence biological activity towards Pseudomonas aeruginosa. The results suggest that coumarin derivatives with a secondary carbon at C-3 position reduces P. aeruginosa growth whereas compounds with one additional substituent have a significant effect over pyocyanin production (10k EC50 7 ± 2 µM; 10l EC50 42 ± 13 µM). Moreover, 10k reduces P. aeruginosa motility and biofilm formation, what is compatible with a quorum sensing related mechanism of action.

Synthesis of New Xanthenes Based on Lawsone and Coumarin via a Tandem Three‑Component Reaction

The synthesis of several new xanthenes based on the 1,3-dicarbonyl scaffolds lawsone and coumarin was developed using tandem three-component reactions involving the reagents ortho-hydroxybenzaldehyde, as bifunctional reagent, and an appropriate thiol. These reactions generated two series of paraand ortho-naphthoxanthenes that are structurally related to αand β-pyranaphthoquinones and one series of coumarin-xanthene derivatives.

Synthetic methodologies leading to porphyrin-quinone conjugates

This review focuses on synthetic strategies that have been established for the preparation of porphyrin-quinone conjugates of potential biological significance and as donor–acceptor compounds for electron transfer processes.