Synthesis and Biological Studies of Benzo[b]furan Derivatives: A Review from 2011 to 2022.

The importance of the benzo[b]furan motif becomes evident in the remarkable results of numerous biological investigations, establishing its potential as a robust therapeutic option. This review presents an overview of the synthesis of and exhaustive biological studies conducted on benzo[b]furan derivatives from 2011 to 2022, accentuating their exceptional promise as anticancer, antibacterial, and antifungal agents. Initially, the discussion focuses on chemical synthesis, molecular docking simulations, and both in vitro and in vivo studies. Additionally, we provide an analysis of the intricate interplay between structure and activity, thereby facilitating comparisons and profoundly emphasizing the applications of the benzo[b]furan motif within the realms of drug discovery and medicinal chemistry.

Versatile Electrochemical Synthesis of Selenylbenzo[b]Furan Derivatives Through the Cyclization of 2-Alkynylphenols.

We report an electrochemical oxidative intramolecular cyclization reaction between 2-alkynylphenol derivatives and different diselenides species to generate a wide variety of substituted-benzo[b]furans. Driven by the galvanostatic electrolysis assembled in an undivided cell, it provided efficient transformation into oxidant-, base-, and metal-free conditions in an open system at room temperature. With satisfactory functional group compatibility, the products were obtained in good to excellent yields.

Applying the Global Monitoring Plan and analysis of POPs results in atmospheric air in Mexico (2017-2018).

Air is one of the target matrices of the Global Monitoring Plan (GMP) of the Stockholm Convention to determine concentrations and transport of Persistent Organic Pollutants (POPs). Mexico participates in the GMP for POPs in ambient air through the AIR-Global Environment Facility (GEF) program. The objective of this study was to analyze the results of POPs monitoring of air samples collected in Los Mochis, Sinaloa, Mexico, between 2017 and 2018. Passive samplers were used for the determination of chlorinated basic POPs, indicator polychlorinated biphenyls (Ind. PCBs), polybrominated biphenyl ethers (PBDEs), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dl-PCBs). A principal component analysis was applied to determine relationships between pollutants and groups present in the ambient air of the rural study area. Of the total POPs analyzed, 85.56% were detected in ambient air samples from Mexico. Organochlorine compounds, as DDT derivatives, were identified mainly, as well as PBDEs, PCDDs, and PCDFs. The prevalence of compounds differed according to the seasonality of sampling, with no change in average concentration between monitoring years.

Evaluation of genetic divergence of coffee genotypes using the volatile compounds and sensory attributes profile.

The quality of the coffee beverage is related to the chemical, physical, and sensory attributes of the coffee beans that vary with the geographic location of the crop, genetic factors, and post-harvest processing. So, the objective of this study was to evaluate the genetic divergence of 27 genotypes of Coffea canephora using the volatile compounds and sensory attributes profile to select genotypes that produce a coffee beverage with high sensory quality. This genetic diversity was estimated from the Euclidean distance matrix using non-standard data and the Unweighted Pair-Group Method Using Arithmetic Averages (UPGMA). The 2-furyl-methanol, 4-ethenyl-2-methoxyphenol, furfural, 5-methylfurfural, methylpyrazine, and 2,6-dimethylpyrazine were predominating volatile compounds in the genotypes. The sensory attributes had a positive Pearson's correlation with the total score. The volatile compounds had a different relative contribution to the genetic divergence between the genotypes of C. canephora. The 4-ethenyl-2-methoxyphenol, 2-furyl-methanol, and furfural were volatile compounds that most contributed to the formation of the groups in the UPGMA dendrogram. The relative contribution of sensory attributes to dissimilarity among genotypes was 6.42% to 20.20%. Therefore, this study verified the relative contribution of volatile compounds, in specially 4-ethenyl-2-methoxyphenol, 2-furyl-methanol, and furfural, and sensory attributes (flavor, mouthfeel, and bitterness/sweetness) to the genetic divergence between the genotypes of the three clonal varieties. Thus, this work points out compounds that positively contribute to the sensory quality of the Conilon coffee beverage.

Widespread distribution of hmf genes in Proteobacteria reveals key enzymes for 5-hydroxymethylfurfural conversion.

Furans represent a class of promising chemicals, since they constitute valuable intermediates in conversion of biomass into sustainable products intended to replace petroleum-derivatives. Conversely, generation of furfural and 5-hydroxymethylfurfural (HMF) as by-products in lignocellulosic hydrolysates is undesirable due its inhibitory effect over fermentative microorganisms. Therefore, the search for furans-metabolizing bacteria has gained increasing attention since they are valuable tools to solve these challenging issues. A few bacterial species have been described at genetic level, leading to a proposed HMF pathway encoded by a set of genes termed hmf/psf, although some enzymatic functions are still elusive. In this work we performed a genomic analysis of major subunits of furoyl-CoA dehydrogenase orthologues, revealing that the furoic acid catabolic route, key intermediate in HMF biodegradation, is widespread in proteobacterial species. Additionally, presence/absence profiles of hmf/psf genes in selected proteobacterial strains suggest parallel and/or complementary roles of enzymes with previously unclear function that could be key in HMF conversion. The furans utilization pattern of selected strains harboring different hmf/psf gene sets provided additional support for bioinformatic predictions of the relevance of some enzymes. On the other hand, at least three different types of transporter systems are clustered with hmf/psf genes, whose presence is mutually exclusive, suggesting a core and parallel role in furans transport in Proteobacteria. This study expands the number of bacteria that could be recruited in biotechnological processes for furans biodetoxification and predicts a core set of genes required to establish a functional HMF pathway in heterologous hosts for metabolic engineering endeavors.

Levels of Polychlorinated Dibenzo-p-Dioxins/Furans (PCDD/Fs) and Dioxin-Like Polychlorinated Biphenyls (DL-PCBs) in Human Breast Milk in Chile: A Pilot Study.

Persistent organic pollutants (POPs) are organic compounds that resist biochemical degradation, moving long distances across the atmosphere before deposition occurs. Our goal was to provide up-to-date data on the levels of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in breast milk from Chilean women and to estimate the exposure of infants due to breast milk consumption. In Chile, we conducted a cross-sectional study based on methodologies proposed by the WHO, with a sample of 30 women recruited from three defined areas: 10 from the Arica Region (urban; Arica and Parinacota Region), 10 from Coltauco (rural; O'Higgins Region), and 10 from Molina (40% rural; Maule Region). High-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC/HRMS) was performed on pooled samples from each area. We calculated equivalent toxic concentrations (WHO-TEQ) based on the current WHO Toxic Equivalency Factors (TEF). The minimum and maximum values of ∑ PCDDs/Fs + DL-PCBs-TEQ were 4.317 pg TEQ/g fat in Coltauco and 6.31 pg TEQ/g fat in Arica. Molina had a total TEQ of 5.50 pg TEQ/g fat. The contribution of PCDD/Fs was approximately five-fold higher than that of DL-PCBs. The Estimated Daily Intake (EDI) of ∑ PCDDs/Fs + DL-PCBs based on the three pooled samples ranged between 6.71 and 26.28 pg TEQ/kg body weight (bw)/day, with a mean intake of 16.11 (±6.71) pg TEQ/kg bw/day in breastfed children from 0 to 24 months old. These levels were lower than those reported in international studies. Despite the fact that the observed levels were low compared to those in most industrialized countries, the detection of a variety of POPs in breast milk from Chilean women indicates the need for follow-up studies to determine whether such exposures during childhood could represent a health risk in adulthood.

Polychlorinated biphenyls are still alarming persistent organic pollutants in marine-origin animal feed (fishmeal).

The presence of polychlorinated biphenyls (PCBs) in feed materials has caused great public concern because PCBs can accumulate in farmed animals, be transferred farm-to-fork and, ultimately, have a detrimental impact on human health. Recently, the occurrence of PCBs in marine environments has garnered scientific attention due to their high levels and potential reproductive threats to marine apex predators. Fishmeal is marine-origin feed material and is susceptible to PCB contamination from the aquatic trophic chain. The present study collected 102 fishmeal samples during 2012-2017 from major global fishmeal production areas (United States, Europe, China, South America and Southeast Asia). The levels of PCBs (26 congeners) were between 0.4 and 19.9 ng g-1 dw (mean: 1.94 ng g-1 dw), with a 75.3% contribution from indicator PCBs on a weight basis. Together with PCDD/Fs, 4.9% of fishmeal exceeded the maximum levels set by the European Commission for dioxin-like compounds (4.0 pg WHO-TEQ/g). The highest PCB levels were found in fishmeal from the U.S. (6.85 ng g-1 dw), which was nearly five times higher than the other four sampling areas. No clear time trends were found for PCBs in fishmeal during the sampling period. Predicted PCB concentrations in farmed fish via fishmeal consumption were between 1.24 and 2.76 ng g-1 dw, which was comparable to PCBs in market fish. When compared to other emerging POPs in the same batches of fishmeal, PCBs were still found to be an alarming class of POPs. Some PCB and PBDE congeners might have similar sources and environmental behaviors.

Fast extraction of polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran in sewage sludge and soil samples.

The current environmental legislations recommend monitoring chemical contaminants such as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans before the use of sewage sludge on the agricultural land. In this study, a solid-liquid extraction with low-temperature purification (SLE-LTP) was optimized and validated to determine 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran in sewage sludge and soil samples. The analyses were performed by gas chromatography-mass spectrometry operating in the selective ion mode (GC-MS-SIM). Acetonitrile:ethyl acetate 6.5:1.5 (v/v) was the best extraction phase, and the recoveries percentages were close to 100%. The linearity was demonstrated in the range of 1.25-25 µg L-1 of 1.25-20 µg L-1 for sewage sludge and soil, respectively. Matrix effect was proved for the two compounds and in the two matrices studied. Extraction percentages were between 78 and 109% and relative standard deviations ≤ 19%. The proposed method is faster than methods described in the literature because showed a few steps. The quantification limits (LOQ) in sewage sludge were 6.4 and 32 ng TEQ kg-1 for 2,3,7,8-TCDF and 2,3,7,8-TCDD, respectively. In soil, LOQs were 0.8 and 8.0 ng TEQ kg-1 for 2,3,7,8-TCDF and 2,3,7,8-TCDD, respectively. These values are lower than the maximum residue limits established by European Legislation. The method was applied to 22 agricultural soil samples from different Brazilian cities and 2,3,7,8-TCDF was detected in one of these samples.

Impact of forest fires on the concentrations of polychlorinated dibenzo-p-dioxin and dibenzofurans in coastal waters of central Chile.

The relationship between the occurrence of forest fires in central Chile and the total concentration of dioxins and furans (PCDD/F) in nearby coastal waters was analyzed. The data for this analysis was obtained from a long-term environmental monitoring program (PROMNA) in the Bio-Bio Region. Quantification of PCDD/F was performed using HRGC/HRMS at the MSS laboratory in England. Between 2006 and 2014, peaks were observed in February 2007 and 2012. These concentration maxima coincided with major forest fires in the Bio-Bio Region and particularly with those in the Itata River Basin. The January 2012 fires generated an intense short-term response that was associated with atmospheric transport which increases medium toxicity furan-type congeners concentrations (TCDF, PCDF and HxCDF) and six months later a concentration increase of low toxicity dioxin-type congeners was observed (OCDD, HpCDD and HxCDD) coinciding with maximum winter river flow. These results suggest that forest fires near the coastal zone are responsible for increases in PCDD/F concentration observed in the study area.

N-(furfural) chitosan hydrogels based on Diels-Alder cycloadditions and application as microspheres for controlled drug release.

In this study, chitosan was chemically modified by reductive amination in a two-step process. The synthesis of N-(furfural) chitosan (FC) was confirmed by FT-IR and (1)H NMR analysis, and the degrees of substitution were estimated as 8.3 and 23.8%. The cross-linkable system of bismaleimide (BM) and FC shows that FC shared properties of furan-maleimide chemistry. This system produced non-reversible hydrogel networks by Diels-Alder cycloadditions at 85 °C. The system composed of BM and FC (23.8% substitution) generated stronger hydrogel networks than those of FC with an 8.3% degree of substitution. Moreover, the FC-BM system was able to produce hydrogel microspheres. Environmental scanning electron microscopy revealed the surface of the microspheres to be non-porous with small protuberances. In water, the microspheres swelled, increasing their volume by 30%. Finally, microspheres loaded with methylene blue were able to release the dye gradually, obeying second-order kinetics for times less than 600 min. This behavior suggests that diffusion is governed by the relaxation of polymer chains in the swelled state, thus facilitating drug release outside the microspheres.

High accumulation of PCDD, PCDF, and PCB congeners in marine mammals from Brazil: a serious PCB problem.

Blubber samples from three delphinid species (false killer whale, Guiana and rough-toothed dolphin), as well as liver samples from franciscana dolphins were analyzed for dioxins and related compounds (DRCs). Samples were collected from 35 cetaceans stranded or incidentally captured in a highly industrialized and urbanized area (Southeast and Southern Brazilian regions). Dioxin-like PCBs accounted for over 83% of the total TEQ for all cetaceans. Non-ortho coplanar PCBs, for franciscanas (82%), and mono-ortho PCBs (up to 80%), for delphinids, constituted the groups of highest contribution to total TEQ. Regarding franciscana dolphins, significant negative correlations were found between total length (TL) and three variables, ΣTEQ-DRCs, ΣTEQ-PCDF and ΣTEQ non-ortho PCB. An increasing efficiency of the detoxifying activity with the growth of the animal may be a plausible explanation for these findings. This hypothesis is reinforced by the significant negative correlation found between TL and PCB126/PCB169 concentration ratio. DRC concentrations (ng/g lipids) varied from 36 to 3006, for franciscana dolphins, as well as from 356 to 30,776, for delphinids. The sum of dioxin-like and indicator PCBs varied from 34,662 to 279,407 ng/g lipids, for Guiana dolphins from Rio de Janeiro state, which are among the highest PCB concentrations ever reported for cetaceans. The high concentrations found in our study raise concern not only on the conservation of Brazilian coastal cetaceans, but also on the possibility of human health problem due to consumption of fish from Brazilian estuaries.