Medicines as an emergent contaminant: the review of microbial biodegration potential.

Emerging environmental contaminants, such as medicine waste, are of great concern to the scientific community and to the local environmental and health departments because of their potential long-term effects and ecotoxicological risk. Besides the prolonged use of medicines for the development of modern society, the elucidation of their effect on the ecosystem is relatively recent. Medicine waste and its metabolites can, for instance, cause alterations in microbial dynamics and disturb fish behavior. Bioremediation is an efficient and eco-friendly technology that appears as a suitable alternative to conventional methods of water waste and sludge treatment and has the capacity to remove or reduce the presence of emerging contaminants. Thus, this review has the objective of compiling information on environmental contamination by common medicines and their microbial biodegradation, focusing on five therapeutic classes: analgesics, antibiotics, antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), and contraceptives. Their effects in the environment will also be analyzed, as well as the possible routes of degradation by microorganisms.

Design, synthesis, in vitro and in silico studies of novel 4-oxoquinoline ribonucleoside derivatives as HIV-1 reverse transcriptase inhibitors.

Human immunodeficiency virus type 1 (HIV-1) is a public health problem that affects over 38 million people worldwide. Although there are highly active antiretroviral therapies, emergence of antiviral resistant strains is a problem which leads to almost a million death annually. Thus, the development of new drugs is necessary. The viral enzyme reverse transcriptase (RT) represents a validated therapeutic target. Because the oxoquinolinic scaffold has substantial biological activities, including antiretroviral, a new series of 4-oxoquinoline ribonucleoside derivatives obtained by molecular hybridization were studied here. All synthesized compounds were tested against human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), and 9a and 9d displayed the highest antiviral activities, with IC50 values of 1.4 and 1.6 µM, respectively. These compounds were less cytotoxic than AZT and showed CC50 values of 1486 and 1394 µM, respectively. Molecular docking studies showed that the most active compounds bound to the allosteric site of the enzyme, suggesting a low susceptibility to the development of antiviral resistance. In silico pharmacokinetic and toxicological evaluations reinforced the potential of the active compounds as anti-HIV candidates for further exploration. Overall, this work showed that compounds 9a and 9d are promising scaffold for future anti-HIV-1 RT drug design.

4-Oxoquinoline Derivatives as Antivirals: A Ten Years Overview.

4-Oxoquinoline derivatives constitute an important family of biologically important substances, associated with different bioactivities, which can be synthesized by different synthetic methods, allowing the design and preparation of libraries of substances with specific structural variations capable of modulating their pharmacological action. Over the last years, these substances have been extensively explored by the scientific community in efforts to develop new biologically active agents, with greater efficiency for the treatment of a variety of diseases. Viral infections have been one of the targets of these studies, although to a lesser extent than other diseases such as cancer and bacterial infections. Nevertheless, the literature provides examples that corroborate with the fact that these substances may act on different pharmacological targets in different viral pathogens. This review provides a compilation of some of the major studies published in recent years showing the discovery and/or development of new antiviral oxoquinoline agents, highlighting, whenever possible, their mechanisms of action.

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide.

4-Oxoquinolines are a class of organic substances of great importance in medicinal chemistry, due to their biological and synthetic versatility. N-1-Alkylated-4-oxoquinoline derivatives have been associated with different pharmacological activities such as antibacterial and antiviral. The presence of a carboxamide unit connected to carbon C-3 of the 4-oxoquinoline core has been associated with various biological activities. Experimentally, the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide occurs at the nitrogen of the oxoquinoline group, in a regiosselective way. In this work, we employed DFT methods to investigate the regiosselective ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide, evaluating its acid/base behavior and possible reaction paths.

Biogenic synthesis of multifunctional silver nanoparticles from Rhodotorula glutinis and Rhodotorula mucilaginosa: antifungal, catalytic and cytotoxicity activities.

Silver nanoparticles (AgNPs) have several technological applications and may be synthetized by chemical, physical and biological methods. Biosynthesis using fungi has a wide enzymatic range and it is easy to handle. However, there are few reports of yeasts with biosynthetic ability to produce stable AgNPs. The purpose of this study was to isolate and identify soil yeasts (Rhodotorula glutinis and Rhodotorula mucilaginosa). After this step, the yeasts were used to obtain AgNPs with catalytic and antifungal activity evaluation. Silver Nanoparticles were characterized by UV-Vis, DLS, FTIR, XRD, EDX, SEM, TEM and AFM. The AgNPs produced by R. glutinis and R. mucilaginosa have 15.45 ± 7.94 nm and 13.70 ± 8.21 nm (average ± SD), respectively, when analyzed by TEM. AgNPs showed high catalytic capacity in the degradation of 4-nitrophenol and methylene blue. In addition, AgNPs showed high antifungal activity against Candida parapsilosis and increase the activity of fluconazole (42.2% for R. glutinis and 29.7% for R. mucilaginosa), while the cytotoxicity of AgNPs was only observed at high concentrations. Finally, two yeasts with the ability to produce AgNPs were described and these particles showed multifunctionality and can represent a technological alternative in many different areas with potential applications.

Impact of UV-C Light on the Fatty Acid Profile and Oxidative Stability of Nile Tilapia (Oreochromis niloticus) Fillets.

The influence of different ultraviolet (UV-C) doses (0.103 and 0.305 J/cm2 ) was investigated by instrumental color parameters, pH, lipid, and protein oxidations, fatty acids (FA) composition and biogenic amines (BAs) in Nile tilapia fillets during 11 d at 4 ± 1 °C. The UV-C treatment increased (P < 0.05) a* values and protein oxidation in a dose-dependent manner, and delayed (P < 0.05) the formation of BAs over the course of the storage period. L* values and lipid oxidation were not influenced (P > 0.05) by UV-C light. Fillets treated with a low UV-C dose exhibited greater (P < 0.05) total polyunsaturated fatty acid (PUFA) than their untreated counterparts. Therefore, a low UV-C dose can be recommended in tilapia fillets as an alternative processing method to control pH and BAs, as well as improve the total PUFA amount and overall nutritional quality.

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.

The application of chiral aminonaphthols in the enantioselective addition of diethylzinc to aryl aldehydes.

[reaction: see text]. Optically active aminonaphthol 3 obtained by condensation of 2-naphthol, benzaldehyde, and (S)-methylbenzylamine followed by N-methylation was found to catalyze the enantioselective ethylation of aryl aldehydes to secondary alcohols with high enantioselectivities (up to 99.8%) at room temperature.