The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse family of compounds that have been isolated from different marine microorganisms. Within the different polyketides, benzophenones, diphenyl ethers, anthraquinones, and xanthones have shown promising antibacterial activity. In this work, a dataset of 246 marine polyketides has been identified. In order to characterize the chemical space occupied by these marine polyketides, molecular descriptors and fingerprints were calculated. Molecular descriptors were analyzed according to the scaffold, and principal component analysis was performed to identify the relationships among the different descriptors. Generally, the identified marine polyketides are unsaturated, water-insoluble compounds. Among the different polyketides, diphenyl ethers tend to be more lipophilic and non-polar than the remaining classes. Molecular fingerprints were used to group the polyketides according to their molecular similarity into clusters. A total of 76 clusters were obtained, with a loose threshold for the Butina clustering algorithm, highlighting the large structural diversity of the marine polyketides. The large structural diversity was also evidenced by the visualization trees map assembled using the tree map (TMAP) unsupervised machine-learning method. The available antibacterial activity data were examined in terms of bacterial strains, and the activity data were used to rank the compounds according to their antibacterial potential. This potential ranking was used to identify the most promising compounds (four compounds) which can inspire the development of new structural analogs with better potency and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.

Magnetite nanoparticles (Fe3O4) functionalized with graphene oxide (GO) have been synthesized through a silanization process of the magnetic nanoparticles with tetraethyl orthosilicate and (3-aminopropyl)triethoxysilane and further coupling of GO. The synthesized nanomaterials have been characterized by several techniques, such as transmission electron microscopy (TEM), and infrared and Raman spectroscopy, which enabled the evaluation of the different steps of the functionalization process. The hybrid nanomaterial has been employed for the extraction of five benzophenones (benzophenone-1, benzophenone-3, 4-hydroxybenzophenone, benzophenone-6 and benzophenone-8) in aqueous samples by dispersive micro-solid phase extraction, combining the magnetic properties of magnetite nanoparticles with the excellent sorption capacity of graphene oxide via hydrophobic interactions with the analytes. The subsequent separation and quantification of the analytes was performed by liquid chromatography with tandem mass spectrometric detection, achieving limits of detection (LODs) in the range 2.5 to 8.2 μg·L-1, with relative standard deviations ranging from 1.3-9.8% and relative recovering in the range 86 to 105%. Positive swimming pool water samples analysed following the developed method revealed the presence of benzophenones in from 14.3 to 39 μg·L-1.

Hypericum elegans is used in Bulgarian folk medicine for treatment of wounds, depression, gastrointestinal and bacterial diseases.

In recent decades, emerging environmental pollutants such as endocrine-disrupting chemicals (EDCs) have become a particular concern. This study examined the association of maternal exposure to benzophenones as one of the EDCs with gestational age and evaluated their effects on birth outcomes including birth weight, birth length, head circumference, and Ponderal Index. We assessed 166 pregnant mothers of the PERSIAN cohort population of Isfahan, Iran, in the 1st and 3rd trimesters of pregnancy and their infants at birth. Four common benzophenones (BPs) including 2,4-dihydroxy benzophenone (BP-1), 2-hydroxy-4-methoxy benzophenone (BP-3), 4-hydroxy benzophenone (4-OH-BP), and 2,2'-dihydroxy-4-methoxy benzophenone (BP-8) were measured in maternal urine samples. The median urinary concentrations of 4-OH-BP, BP-3, BP-1, and BP-8 in the 1st trimester were 6.62, 7.5, 4.39, and 1.32 µg/g creatinine and those in the 3rd trimester were 3.15, 16.98, 9.95, and 1.04 µg/g creatinine, respectively. BP-3 was the predominant metabolite in both trimesters. There was a significant correlation between BP-3, BP-1, and 4-OH-BP levels (p < 0.05) but not BP-8. BP-1 showed a significant positive association with gestational age (GA) in all infants in the 1st trimester, but a negative association was observed between BP-3 and BP-1 levels and GA in girls. Classification of infants' birth weight for different GAs represented that the majority of them were appropriate for GA. However, boys' weights were heavier than girls. Also, birth outcomes of preterm (< 37 weeks) infants were noticeably lower than term infants (37-42 weeks). This study demonstrated that benzophenone derivatives especially BP-3 can affect the duration of pregnancy and consequently fetal growth in the early and late stages of pregnancy. This is more pronounced in girls; however, more investigations in a different population are needed to prove the results. Therefore, the application of these compounds as a UV protector requires precise regulation to reduce exposure, especially in pregnant women.

This study aimed to isolate polyprenylated benzophenones from the rootbark of Garcinia celebica and assess their activities in vitro and in silico. The antioxidant activity was evaluated by the DPPH, ABTS, and FRAP methods. The cytotoxicity was evaluated against HeLa, MCF-7, A549, and B16 cancer cell lines. The antiplasmodial activity was performed against the chloroquine-sensitive Plasmodium falciparum strain 3D7. Molecular docking was analyzed on alpha-estrogen receptor (3ERT) and P. falciparum lactate dehydrogenase enzyme (1CET). The prediction of ADMET for the compounds was also studied. For the first time, (-)-cycloxanthochymol, isoxanthochymol, and xanthochymol were isolated from the root bark of Garcinia celebica. The antioxidant and cytotoxicity evaluation showed that all benzophenones exhibited antioxidant activity compared to gallic acid and quercetin as positive controls and also exhibited strong activity against HeLa, MCF-7, A549, and B16 cell lines compared to cisplatin as the positive control. The antiplasmodial evaluation showed that isoxanthochymol exhibited activity against the chloroquine-sensitive P. falciparum strain 3D7. In addition, the in silico molecular docking study supported in vitro activities. The ADMET analysis also indicated the isolated benzophenones are potential oral drug candidates.

A convenient method of applying competition experiments to devise a Hammett correlation in the dissociation by α-cleavage of 17 ionised 3- and 4-substituted benzophenones, YC6H4COC6H5 [Y=F, Cl, Br, CH3, CH3O, NH2, CF3, OH, NO2, CN and N(CH3)2] is reported and discussed. The results given by this approach, which rely on the relative abundance of [M-C6H5]+ and [M-C6H4Y]+ ions in the electron ionisation spectra of the substituted benzophenones, are compared with those obtained by previous methods. Various refinements of the method are considered, including reducing the ionising electron energy, making allowance for the relative abundance of ions such as C6H5+ and C6H4Y+, which may be formed to some extent by secondary fragmentation, and using substituent constants other than the standard σ constants. The reaction constant, ρ, of 1.08, which is in good agreement with that deduced previously, is consistent with a considerable reduction in electron density (corresponding to an increase in positive charge) at the carbon of the carbonyl group during fragmentation. This method has been successfully extended to the corresponding cleavage of 12 ionised substituted dibenzylideneacetones, YC6H4CH=CHCOCH=CHC6H5 (Y=F, Cl, CH3, OCH3, CF3, and NO2), which may fragment to form either a substituted cinnamoyl cation, [YC6H4CH=CHCO]+, or the cinnamoyl cation, [C6H5CH=CHCO]+. The derived ρ value of 0.76 indicates that the substituent, Y, influences the stability of the cinnamoyl cation somewhat less strongly than it does the analogous benzoyl cation.

Liver cancer refers primarily to hepatocellular carcinoma (HCC) accounting for over 90% of cases and is the highest incidence in men in Thailand. Over the past decades, the incidence of HCC dramatically increased with a strong rise of mortality rates. Garcinia mangostana, "Queen of Fruit" of Thailand, is known as a rich source of xanthones with potent cytotoxic properties against various cancer cells. Study on xanthones is provoking not only due to the structural diversity but also a wide variety of pharmacological activities. Hence the aim of the current study is to determine the effects of metabolites from G. mangostana root on cell proliferation and migration of hepatocellular carcinoma cells. Twenty-two metabolites, including two new benzophenones and one new biphenyl, were isolated and characterized. Five xanthones with a prenyl moiety showed significant cytotoxicity against both HCC cells tested; however, only dulxanthone D displayed the most promising activity on the migration of Huh7 HCC cells, comparable to sorafenib, a standard drug. Moreover, the compound dose-dependently induced apoptosis in Huh7 cells via mitochondrial pathway. Accordingly, dulxanthone D held a great potential for development as a novel migration inhibitor for effective HCC treatment.

A chemical investigation of the fibrous roots of Anemarrhena asphodeloides Bge. led to the isolation of four benzophenones, including one new compound (1) and three known ones (2-4). Comprehensive 1D, 2D NMR and HRESIMS data established the structures of the isolated compounds. The absolute configurations were determined by comparison of the calculated optical rotation (OR) with experimental data. All the isolates were evaluated for their cytotoxicities on hepatocellular carcinoma cell lines (HepG2 and Hep3B). Compound 1 showed strong cytotoxicity against HepG2 and Hep3B cells, with IC50 values at 153.1 and 180.6 nM. Through MTT assay, flow cytometry and Western blot analysis, compound 1 demonstrated the ability to stimulate apoptosis via the NF-κB signaling pathway in HepG2 cells. These benzophenones are potential lead compounds for the development of better treatments for hepatocellular carcinoma.

Humans could be exposed to ingredients in personal care products (PCPs) via ingestion of water originated from contaminated water source, yet little attention has been focused on the distribution of benzophenones, parabens and triclosan in the Yangtze River water from China so far. Benzophenones, parabens and triclosan were analyzed in the water samples from 20 various sites in the middle reach of the Yangtze River, China from March to July, and September during 2015. Among the targeted compounds, p-hydroxybenzoic acid (PHBA, a paraben metabolite) was found with the highest concentration (median: 510 ng/L), followed by benzophenone-1 (2.79 ng/L), methylparaben (MeP, median 2.72 ng/L) and triclosan (median: 1.85 ng/L). Significant differences were observed in seasonal variations for most observed compounds. Parabens and benzophenones showed higher concentrations in spring while triclosan and PHBA showed higher concentration in summer. Spatial variations of benzophenone-1 were observed among 20 sampling sites, whereas other benzophenones, parabens and triclosan distributed evenly comparatively. Human exposure assessment showed higher estimated daily intake of the detected compounds for infants and toddlers from water than adults, implicating that infants may experience a higher exposed risk than adults. This study provides evidence that parabens, benzophenones and triclosan commonly occurred in the Yangtze River.

To explore the relationship of urinary concentrations of different congeners of benzophenones and parabens with the utilization of cosmetics and personal care products (PCPs) and their impact on the risk of endometriosis, and to evaluate the influence of oxidative stress on associations found.

Benzophenones (BPs) are extensively used in a wide variety of cosmetic products and other materials (e.g., textiles or plastics) to avoid damaging effects of UV radiation. In the present work, we compared two extraction methods for the determination of BPs, namely, 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 2,2-dihydroxy-4-methoxybenzophenone (BP-8), in water and cosmetics samples. The following extraction methods were used for the research: solid-phase extraction (SPE) and microextraction by packed sorbent (MEPS), whereas analysis was performed by gas chromatography with mass spectrometric detection. A comparison between the methods indicates that the MEPS technique(s) can be reliably used for analysis of BPs (sunscreen residue) in water samples and cosmetic samples with satisfactory results. This microextraction technique is cheap, easy, quick to implement, and consumes small amounts of solvents. On the other hand, the main advantage of the SPE method are low detection limits for the determination of BPs in water samples, i.e., from 0.034 to 0.067 µg L-1, while, for the MEPS method, LODs were at the level of 1.8-3.2 µg L-1. For both methods, the recoveries of BPs were 96-107% and 44-70% for water and cosmetics samples, respectively. The presented methods are suitable for use in cosmetics quality control and environmental pollution assessment.

Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities. In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity. Garcinia parvifolia is used in traditional medicine. Currently, the antiviral activity of G. parvifolia is not known.

The MDR-involved human GSTA1-1, an important isoenzyme overexpressed in several tumors leading to chemotherapeutic-resistant tumour cells, has been targeted by 2,2'-dihydroxybenzophenones and some of their carbonyl N-analogues, as its potential inhibitors. A structure-based library of the latter was built-up by a nucleophilic cleavage of suitably substituted xanthones to 2,2'-dihydroxy-benzophenones (5-9) and subsequent formation of their N-derivatives (oximes 11-13 and N-acyl hydrazones 14-16). Screening against hGSTA1-1 led to benzophenones 6 and 8, and hydrazones 14 and 16, having the highest inhibition potency (IC₅₀ values in the range 0.18 ± 0.02 to 1.77 ± 0.10 μM). Enzyme inhibition kinetics, molecular modeling and docking studies showed that they interact primarily at the CDNB-binding catalytic site of the enzyme. In addition, the results from cytotoxicity studies with human colon adenocarcinoma cells showed low LC₅₀ values for benzophenone 6 and its N-acyl hydrazone analogue 14 (31.4 ± 0.4 μM and 87 ± 1.9 μM, respectively), in addition to the strong enzyme inhibition profile (IC₅₀(6)=1,77 ± 0.10 μM; IC₅₀(14)=0.33 ± 0.05 μM). These structures may serve as leads for the design of new potent mono- and bi-functional inhibitors and pro-drugs against human GTSs.

Major concerns have been raised about human exposure to endocrine-disrupting chemicals (EDCs) during pregnancy. Effective methodologies for the assessment of this exposure are needed to support the implementation of preventive measures and the prediction of negative health effects. Meconium has proven a valuable non-invasive matrix for evaluating cumulative exposure to xenobiotics during the last two trimesters of pregnancy. The study objective was to develop a novel method to determine the presence in meconium of perfluoroalkyl substances (PFASs), bisphenols, parabens, and benzophenones, EDCs that are widely used in the manufacture of numerous consumer goods and personal care products, including cosmetics. Ten PFASs, two bisphenols, four parabens, and four benzophenones were measured in meconium samples prepared by using a combination of Captiva Enhanced Matrix Removal (EMR) lipid cartridges with salt-assisted liquid-liquid extraction (SALLE) and dispersive liquid-liquid microextraction (DLLME) before the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Experimental parameters were optimized by applying different chemometric techniques. Limits of detection ranged from 0.05 to 0.1 ng g-1, and between-day variabilities (relative standard deviations) ranged from 6.5% to 14.5%. The method was validated by matrix-matched standard calibration followed by a recovery assay with spiked samples, obtaining percentage recoveries of 89.9% to 114.8%. The method was then employed to measure compounds not previously studied in this matrix in 20 meconium samples. The proposed analytical procedure yields information on cumulative in utero exposure to selected EDCs.

Breast cancer is the cause of considerable morbidity and mortality in women. While estrogen receptor antagonists have been widely used in breast cancer treatment, patients have increasingly shown resistance to these agents and the identification of novel targeted therapies is therefore required. Nemorosone is the major constituent of the floral resin from Clusia rosea and belongs to the class of polycyclic polyisoprenylated benzophenones of the acylphloroglucinol group. The cytotoxicity of nemorosone in human cancer cell lines has been reported in recent years and has been related to estrogen receptors in breast cancer cells.

The synthesis of hydroxy benzophenones and benzophenone-N-ethyl morpholine ethers and the results of anti-inflammatory activity in vivo are described. The structures of the compounds were elucidated by IR, (1)H-NMR, mass spectroscopy and the elementary analysis. The anti-inflammatory activity of the synthesized compounds were determined by carrageenan-induced hind paw oedema test in rats. Most of the tested compounds exhibited anti-inflammatory activity and some of them were more active than standard drugs. In addition ulcerogenic and cyclooxygenase activities are also described.

Chemical cross-linking mass-spectrometry (XL-MS) represents a powerful methodology to map ligand/biomacromolecule interactions, particularly where conventional methods such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy or cryo-electron microscopy (EM) are not feasible. In this manuscript, we describe the design and synthesis of two new photo-crosslinking reagents that can be used to specifically label free thiols through either maleimido or methanethiosulfonate groups and facilitate PXL-MS workflows. Both crosslinkers are based on light sensitive diazirines - precursors of highly reactive carbenes which offer additional advantages over alternative crosslinking groups such as benzophenones and aryl nitrenes given the controlled rapid and more indiscriminate reactivity.

The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug resistance (MDR) in tumors as well as to influence ADME properties of drug candidates. Here we synthesized and tested a series of benzophenone derivatives structurally analogous to propafenone-type inhibitors of P-gp. Some of the compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the range of compounds which entered clinical trials as MDR modulators. Interestingly, although lipophilicity plays a dominant role for P-gp inhibitors, all compounds investigated showed LipE values below the threshold for promising drug candidates. Docking studies of selected analogues into a homology model of P-glycoprotein suggest that benzophenones show an interaction pattern similar to that previously identified for propafenone-type inhibitors.

Six compounds including three new benzophenones, selagibenzophenones D-F (1-3), two known selaginellins (4-5) and one known flavonoid (6), were isolated from Selaginella tamariscina. The structures of new compounds were established by 1D-, 2D-NMR and HR-ESI-MS spectral analyses. Compound 1 represents the second example of diarylbenzophenone from natural sources. Compound 2 possesses an unusual biphenyl-bisbenzophenone structure. Their cytotoxicity against human hepatocellular carcinoma HepG2 and SMCC-7721 cells and inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells were evaluated. Compound 2 showed moderate inhibitory activity against HepG2 and SMCC-7721 cells, and compounds 4 and 5 showed moderate inhibitory activity to HepG2 cells. Compounds 2 and 5 also exhibited inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production.

A device comprising a zirconium-based metal-organic framework (MOF) mixed-matrix membrane (MMM) framed in a plastic holder has been used to monitor the content of personal care products (PCPs) in cosmetic samples. Seven different devices containing the porous frameworks UiO-66, UiO-66-COOH, UiO-67, DUT-52, DUT-67, MOF-801, and MOF-808 in polyvinylidene fluoride (PVDF) membranes were studied. Optimized membranes reach high adsorption capacities of PCPs, up to 12.5 mg·g-1 benzophenone in a 3.0 mg·L-1 sample. The MMM adsorption kinetics, uptake measurements, and isotherm studies were carried out with aqueous standard solutions of PCPs to ensure complete characterization of the performance. The studies demonstrate the high applicability and selectivity of the composites prepared, highlighting the performance of PVDF/DUT-52 MMM that poses uptakes up to 78% for those PCPs with higher affinity while observing detection limits for the entire method down to 0.03 μg·L-1. The PVDF/DUT-52 device allowed the detection of parabens and benzophenones in the samples, with PCPs found at concentrations of 1.9-24 mg·L-1.