3-Imino derivative-sulfahydantoins: Synthesis, in vitro antibacterial and cytotoxic activities and their DNA interactions.

Sulfahydantoins are five-membered rings found in the structure of chemicals that exhibit antibacterial, anti-inflammatory, and anticonvulsant properties. They also activate serine protease enzymes that catalyze the hydrolysis of peptide bonds. Five 3-imino sulfahydantoin compounds were synthesized by using Strecker synthesis reaction with minor modifications. We used reflux of various aldehydes with excess sulfamide in 85% methanol in the presence of sodium cyanide. The spectroscopic properties of these compounds were studied in detail. Antibacterial activities of all synthesized new compounds against four Gram-positive (Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Streptococcus mutans) and four Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella Enteritidis) bacteria were investigated by disc diffusion and microdilution method. pBR322 plasmid DNA binding abilities of compounds were investigated in vitro by agarose gel electrophoresis. In addition, the cytotoxic activities of the compounds against the human malignant pleural mesothelioma (SPC212) cell line were determined by the MTT method. The remarkable result in this study is that the synthesized compounds, especially 4b, 4d, and 4e, have significant biological activities. It has been demonstrated that these compounds, which cause DNA damage, also have an important antibacterial effect on both Gram-negative and Gram-positive bacteria when results compared with the control group antibiotics. Compound 4e exhibited the highest antibacterial potency against Streptococcus mutans (24.33 ± 0.57) from Gram-positive bacteria and Pseudomonas aeruginosa (24.66 ± 1.15) from Gram-negative bacteria. At the same time, MTT results determined that compounds 4b, 4d, and 4e showed cytotoxic activity against the SPC212 cells. In particular, compound 4b had a high cytotoxic effect, and the IC50 value was determined as 6.25 µM.

Hemimycalins C-E; Cytotoxic and Antimicrobial Alkaloids with Hydantoin and 2-Iminoimidazolidin-4-one Backbones from the Red Sea Marine Sponge Hemimycale sp.

In the course of our continuing efforts to identify bioactive secondary metabolites from Red Sea marine sponges, we have investigated the sponge Hemimycale sp. The cytotoxic fraction of the organic extract of the sponge afforded three new compounds, hemimycalins C-E (1-3). Their structural assignments were obtained via analyses of their one- and two-dimensional NMR spectra and HRESI mass spectrometry. Hemimycalin C was found to differ from the reported hydantoin compounds in the configuration of the olefinic moiety at C-5-C-6, while hemimycalins D and E were found to contain an 2-iminoimidazolidin-4-one moiety instead of the hydantoin moiety in previously reported compounds from the sponge. Hemimycalins C-E showed significant antimicrobial activity against Escherichia coli and Candida albicans and cytotoxic effects against colorectal carcinoma (HCT 116) and the triple-negative breast cancer (MDA-MB-231) cells.

Design, Synthesis, Characterization, and Biological Activities of Novel Spirooxindole Analogues Containing Hydantoin, Thiohydantoin, Urea, and Thiourea Moieties.

On the basis of the scaffolds widely used in drug design, a series of novel spirooxindole derivatives containing hydantoin, thiohydantoin, urea, and thiourea moieties have been designed, synthesized, characterized, and first evaluated for their biological activities. The diastereoselectivity mechanism is proposed, and the systematic conformational analysis is performed. The bioassay results show that the target compounds possess moderate to good antiviral activities against tobacco mosaic virus (TMV), among which compound 22 shows the highest antiviral activity in vitro as well as inactivation, curative, and protection activities in vivo (45 ± 1, 47 ± 3, 50 ± 1, and 51 ± 1%, 500 mg/L, respectively), higher than ribavirin (38 ± 1, 36 ± 1, 38 ± 1, and 36 ± 1%, 500 mg/L, respectively). Thus, compound 22 is a promising candidate for anti-TMV development. Most of these compounds show broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi and selective fungicidal activities against Physalospora piricola, Sclerotinia sclerotiorum, and Rhizoctonia cerealis. Additionally, some of these compounds exhibit insecticidal activity against Culex pipiens pallens, Mythimna separata, Helicoverpa armigera, and Pyrausta nubilalis. Compound 17 exhibits the highest larvicidal activity (LC50 was 0.32 mg/L) against C. pipiens pallens.

Structural basis for the stabilization of amyloidogenic immunoglobulin light chains by hydantoins.

Misfolding and aggregation of immunoglobulin light chains (LCs) leads to the degeneration of post-mitotic tissue in the disease immunoglobulin LC amyloidosis (AL). We previously reported the discovery of small molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which slow or stop the LC aggregation cascade at the outset. A predominant structural category of kinetic stabilizers emerging from the high-throughput screen are coumarins substituted at the 7-position, which bind at the interface between the two variable domains of the light chain dimer. Here, we report the binding mode of another, more polar, LC kinetic stabilizer chemotype, 3,5-substituted hydantoins. Computational docking, solution nuclear magnetic resonance experiments, and x-ray crystallography show that the aromatic substructure emerging from the hydantoin 3-position occupies the same LC binding site as the coumarin ring. Notably, the hydantoin ring extends beyond the binding site mapped out by the coumarin hits. The hydantoin ring makes hydrogen bonds with both LC monomers simultaneously. The alkyl substructure at the hydantoin 5-position partially occupies a novel binding pocket proximal to the pocket occupied by the coumarin substructure. Overall, the hydantoin structural data suggest that a larger area of the LC variable-domain-variable-domain dimer interface is amenable to small molecule binding than previously demonstrated, which should facilitate development of more potent full-length LC kinetic stabilizers.

Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma.

Multidrug resistance (MDR) in cancer cells is a crucial aspect to consider for a successful cancer therapy. P-gp/ABCB1, a member of ABC transporters, is involved in the main tumour MDR mechanism, responsible for the efflux of drugs and cytotoxic substances. Herein, we describe a discovery of potent selenium-containing ABCB1 MDR efflux pump modulators with promising anticancer activity. On three groups of selenoethers comprehensive studies in terms of design, synthesis, and biological assays, including an insight into cellular mechanisms of anticancer action as well as an ADMET-screening in vitro were performed, followed by in-depth SAR analysis. Among the investigated new phenylselenoether hybrids, four compounds showed significant cytotoxic and anti-proliferative effects, in particular, in resistant cancer cells. Hydantoin derivatives (5-7) were significantly more effective than the reference inhibitor verapamil (up to 2.6-fold at a 10-fold lower concentration) modulating ABCB1-efflux pump, also possessing a good drug-drug interaction profile. The best compound (6) was further evaluated in human JURKAT T-lymphocytic cancer cells for its impact on cell proliferation rate. Mechanistically, the expression of cyclin D1, an enhancer of the cell cycle, decreases, while p53, an inhibitor of cell proliferation, was up-regulated upon the treatment with compound 6 alone or in combination with the chemotherapeutic agent doxorubicin. In summary, a new chemical space of highly active selenium-containing anticancer agents has been discovered, with a new lead compound 6 that warrants more in-depth biological evaluation and further pharmacomodulation.

Optimization of Hydantoins as Potent Antimycobacterial Decaprenylphosphoryl-ß-d-Ribose Oxidase (DprE1) Inhibitors.

In search of novel drugs against tuberculosis, we previously discovered and profiled a novel hydantoin-based family that demonstrated highly promising in vitro potency against Mycobacterium. tuberculosis. The compounds were found to be noncovalent inhibitors of DprE1, a subunit of decaprenylphosphoryl-ß-d-ribose-2'-epimerase. This protein, localized in the periplasmic space of the mycobacterial cell wall, was shown to be an essential and vulnerable antimycobacterial drug target. Here, we report the further SAR exploration of this chemical family through more than 80 new analogues. Among these, the most active representatives combined submicromolar cellular potency and nanomolar target affinity with balanced physicochemical properties and low human cytotoxicity. Moreover, we demonstrate in vivo activity in an acute Mtb infection model and provide further proof of DprE1 being the target of the hydantoins. Overall, the hydantoin family of DprE1 inhibitors represents a promising noncovalent lead series for the discovery of novel antituberculosis agents.

RNA polymerase II stalls on oxidative DNA damage via a torsion-latch mechanism involving lone pair-π and CH-π interactions.

Oxidation of guanine generates several types of DNA lesions, such as 8-oxoguanine (8OG), 5-guanidinohydantoin (Gh), and spiroiminodihydantoin (Sp). These guanine-derived oxidative DNA lesions interfere with both replication and transcription. However, the molecular mechanism of transcription processing of Gh and Sp remains unknown. In this study, by combining biochemical and structural analysis, we revealed distinct transcriptional processing of these chemically related oxidized lesions: 8OG allows both error-free and error-prone bypass, whereas Gh or Sp causes strong stalling and only allows slow error-prone incorporation of purines. Our structural studies provide snapshots of how polymerase II (Pol II) is stalled by a nonbulky Gh lesion in a stepwise manner, including the initial lesion encounter, ATP binding, ATP incorporation, jammed translocation, and arrested states. We show that while Gh can form hydrogen bonds with adenosine monophosphate (AMP) during incorporation, this base pair hydrogen bonding is not sufficient to hold an ATP substrate in the addition site and is not stable during Pol II translocation after the chemistry step. Intriguingly, we reveal a unique structural reconfiguration of the Gh lesion in which the hydantoin ring rotates ∼90° and is perpendicular to the upstream base pair planes. The perpendicular hydantoin ring of Gh is stabilized by noncanonical lone pair-π and CH-π interactions, as well as hydrogen bonds. As a result, the Gh lesion, as a functional mimic of a 1,2-intrastrand crosslink, occupies canonical -1 and +1 template positions and compromises the loading of the downstream template base. Furthermore, we suggest Gh and Sp lesions are potential targets of transcription-coupled repair.

Low-cost sugarcane bagasse and peanut shell magnetic-composites applied in the removal of carbofuran and iprodione pesticides.

In the present study, two agro-industrial wastes, sugarcane bagasse, and peanut shell were employed as support of magnetite nanoparticles for the synthesis of magnetic bio-composites: magnetic sugarcane bagasse (MBO) and magnetic peanut shell (MPSo). The presence of magnetite was verified by Raman spectroscopy. Magnetic nanoparticles shape and size distribution were studied by TEM, while composites morphologies were observed by SEM. Structural characteristics of the pesticides and their possible chemical adsorption on composites were analyzed by FTIR. The removal was carried out by a batch adsorption process, and UV-VIS technique was used for pesticide concentration estimation. Elovich model described better all systems pointing out to a chemical adsorption process occurring. Experimental data isotherms of carbofuran and iprodione can be best explained by more than one mathematical model, but Sip was the ordinary equation in all systems. Maximum adsorption capacities of 175 and 89.3 mg/g for carbofuran, and 119 and 2.76 mg/g for iprodione, were obtained for MBo and MPSo, respectively.

Design, synthesis and anticancer evaluation of ß-carboline-1-one hydantoins.

Aim: Cancer is a major health burden and a leading cause of death worldwide. We sought to discover potential anticancer molecules with novel scaffold for further development of more active agents to address the issue. Methodology: A series of ß-carboline-1-one hydantoins were designed according to a conformational restriction strategy, synthesized via a one-pot Knoevenagel condensation-intramolecular cyclization, and tested in cytotoxicity assays. Results: The study culminated in the identification of 6b and 6c, both of which were found to potently inhibit breast and lung cancer cell lines. Of particular interest was 6c, which was 83 times more potent an inhibitor than 5-fluorouracil in inhibiting MCF-7. Conclusion: This work establishes ß-carboline-1-one hydantoin as a promising scaffold in the investigation of anticancer agents.

Anti-Tumor Mechanisms of Novel 3-(4-Substituted Benzyl)-5-Isopropil-5- Phenylhydantoin Derivatives in Human Colon Cancer Cell Line.

BACKGROUND: Hydantoin and its newly synthesized derivatives have recently become a focus of interest due to their numerous biological activities and newly emerging beneficial effects in different pathological conditions, including cancer. OBJECTIVE: The aim of this study was to evaluate the possible anti-tumor mechanisms of a series of newly synthesized 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives in different aspects of cell physiology of human colon cancer cell line, HCT-116. METHODS: The increasing concentrations of derivatives (0.01µM up to 100µM) were applied to cells during 24h, 48h, and 72h after which the evaluation of proliferation, apoptosis, oxidative/anti-oxidative status, nitrite production, and migration/invasion potential of treated cells was performed. RESULTS: All tested compounds expressed the dose- and time-dependent anti-proliferative and pro-apoptotic activities against HCT-116 cells. The investigated derivatives induced a decrease in levels of oxidative stress parameters and an increase in levels of nitrite production by treated cells suggesting their significant antioxidative effects. The cell migration index and expression level of tumor invasion-promoting metalloproteinase- 9 (MMP-9) gene were significantly decreased after treatment with the tested hydantoin derivatives implicating their inhibitory role in colon cancer cell motility and invasion processes. The mRNA level of cyclooxygenase-2 (COX-2) gene as a pro-inflammatory gene related to colorectal carcinogenesis was reduced compared to values in the non-treated control cells indicating the significant anti-inflammatory/anti-tumor effects of these compounds. CONCLUSION: The obtained results show the significant anti-tumor potential of tested derivatives, especially 3- benzyl-5-isopropyl-5-phenylhydantoin and 3-(4-chlorobenzyl)-5-isopropyl-5-phenylhydantoin, suggesting their potential usage in the development of more effective chemotherapies.

Anti-proliferative Activities of Some Bivalent Symmetrical 5-Substituted Hydantoin Derivatives towards Human Brain Glioma U251 Cells (U251) and Human Carcinoma Cells (KB3-1).

Novel bivalent twin-drug type hydantoin derivatives were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the 5-substituted hydantoin derivatives (1a-b and 2a-d) examined in this study, bivalent symmetrical 5-substituted hydantoin derivative 1b showed the highest anti-proliferative activity towards both U251 and KB3-1 cells. The values of anti-proliferative activity (IC50) of this hydantoin derivative against the two cell lines (U251 and KB3-1) were 0.46 and 5.21 µM, respectively. The anti-proliferative activity of all of the compounds except for compounds 2a and 2d against U251 cells was higher than that of cisplatin. Bivalent symmetrical compound 1b had a biphenylmethane linker in the molecule. All of the tested bivalent hydantoin derivatives showed higher activity against U251 cells than against KB3-1 cells. For twin-drug type hydantoin derivatives 2a-d, which have a linear methylene linker in the molecules, it was found that methylene linker length in these molecules have an effect on the anti-proliferative activity against U251 and KB3-1 cells.

Thiohydantoin and Hydantoin Derivatives from the Roots of Armoracia rusticana and Their Neurotrophic and Anti-neuroinflammatory Activities.

Two new thiohydantoins (1 and 3) and three new hydantoins (2, 4, and 5) along with three known compounds (6-8) were isolated from roots of horseradish. Physical data analysis including NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), HRESIMS, and ECD were employed for structure elucidation of the new compounds 1-5. Potential neuroprotective effects of all compounds (1-8) on nerve growth factor (NGF) induction in C6 glioma were also evaluated. Among these compounds, 1b and 2a exhibited potent NGF secretion stimulation activities (NGF secretion levels: 153.59 ± 5.44% and 141.99 ± 5.21%, respectively). Their anti-neuroinflammatory activities were also assessed based on their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide-stimulated murine microglia. Compound 7 marginally inhibited NO production with an IC50 value of 32.6 µM.

Discovery of Novel UV-Filters with Favorable Safety Profiles in the 5-Arylideneimidazolidine-2,4-dione Derivatives Group.

Effective protection from the harmful effects of UV radiation may be achieved by using sunscreens containing organic or inorganic UV filters. The number of currently available UV filters is limited and some of the allowed molecules possess limitations such as systemic absorption, endocrine disruption properties, contact and photocontact allergy induction, and low photostability. In the search for new organic UV filters we designed and synthesized a series consisting of 5-benzylidene and 5-(3-phenylprop-2-en-1-ylidene)imidazolidine-2,4-dione (hydantoin) derivatives. The photoprotective activity of the tested compounds was confirmed in methanol solutions and macrogol formulations. The most promising compounds possessed similar UV protection parameter values as selected commercially available UV filters. The compound diethyl 2,2'-((Z)-4-((E)-3-(4-methoxyphenyl)allylidene)-2,5-dioxoimidazolidine-1,3-diyl)diacetate (4g) was characterized as an especially efficient UVA photoprotective agent with a UVA PF of 6.83 ± 0.05 and favorable photostability. Diethyl 2,2'-((Z)-4-(4-methoxybenzylidene)-2,5-dioxo- imidazolidine-1,3-diyl)diacetate (3b) was the most promising UVB-filter, with a SPFin vitro of 3.07 ± 0.04 and very good solubility and photostability. The main photodegradation products were geometric isomers of the parent compounds. These compounds were also shown to be non-cytotoxic at concentrations up to 50 µM when tested on three types of human skin cells and possess no estrogenic activity, according to the results of a MCF-7 breast cancer model.

Copper-Promoted C-Se Cross-Coupling of 2-Selenohydantoins with Arylboronic Acids in an Open Flask.

The modification of Chan-Lam-Evans cross-coupling reaction for the selective Se-arylation of 2-selenohydantoins under base-free mild conditions via aryl boronic acids is described herein. This approach was used to synthesize novel 5-arylidene-3-substituted-2-(arylselanyl)-imidazoline-4-ones with high yields. The anticancer activity of the final compounds was evaluated in vitro against different cancer cells, and thus, the possibility of 5-arylidene-3-substituted-2-(arylselanyl)-imidazoline-4-ones successful application as cytotoxic agents was demonstrated.

QSAR Analysis of a Series of Hydantoin-based Androgen Receptor Modulators and Corresponding Binding Affinities.

Androgen receptor (AR), a member of the nuclear hormone receptor superfamily of intracellular ligand-dependent transcription factors, plays an indispensable role in normal male development through the regulation of androgen through the binding with endogenous androgens. Inappropriate amounts of androgens have a severe adverse effect on men. Excessive androgen may contribute to accelerate prostatic hypertrophy, even prostate cancer, while the absence of androgen may result in reduced muscle mass and strength, decreased bone mass, low energy, diminished sexual function and an increased risk of osteoporosis and fracture. In these cases, androgen receptor modulators are important to maintain the normal biological function of AR. So androgen receptor modulators are necessary for human being to improve their happy life index. To explore the relationships between molecular structures and corresponding binding abilities to aid the new AR modulator design, multiple linear regressions (MLR) are employed to analyze a series of hydantoin analogues, which can bind to androgen receptor acting as AR modulators. The obtained optimum model presents wonderful reliabilities and strong predictive abilities with R2 =0.858, QLOO2 =0.822, QLMO2 =0.813, QF12 =0.840, QF22 =0.807, QF32 =0.814, CCC=0.893, respectively. The derived model can be used to predict the binding abilities of unknown chemicals and may help to design novel molecules with better AR affinity activity.

QSAR characterization of new synthesized hydantoins with antiproliferative activity.

Hydantois have been identified as constituents of a number of pharmacologically active molecules. In the present study, we have examined in vitro antiproliferative activity against human colon cancer cell lines HCT-116 of three series of 3-(4-substituted benzyl)-hydantoins with various substituent attached in position 5 of the hydantoin ring. Since the investigated compounds have recently been synthesized and show antiproliferative activity, a good understanding of the properties of the potential drug responsible for their pharmacokinetics is an important goal for their further development. One of the important properties is lipophilicity. Lipophilicity has been assessed by reversed-phase liquid chromatography (high-performance thin-layer chromatography and high-pressure liquid chromatography) by means of direct and indirect (using calibration curve) methods. Chromatographic lipophilicity indices in addition to calculated logP values were compared by hierarchical cluster analysis. The linear solvation energy relationship approach was used to understand and compare the types and relative strength of the molecular interactions that occur in the chromatographic as well as in the n-octanol-water partitioning systems. Finally, correlation between in silico pharmacokinetic predictors and antiproliferative activity was examined. Preliminary quantitative structure-activity relationship modeling indicates that pharmacokinetic predictors capture only one-quarter of all chemical features that are important for antiproliferative activity itself. Among selected descriptors are chromatographic lipophilicity indices.

Synthesis, Spectroscopic Properties, Crystal Structure And Biological Evaluation of New Platinum Complexes with 5-methyl-5-(2-thiomethyl)ethyl Hydantoin.

BACKGROUND: The accidental discovery of Cisplatin's growth-inhibiting properties a few decades ago led to the resurgence of interest in metal-based chemotherapeutics. A number of well-discussed factors such as severe systemic toxicity and unfavourable physicochemical properties further limit the clinical application of the platinating agents. Great efforts have been undertaken in the development of alternative platinum derivatives with an extended antitumor spectrum and amended toxicity profile as compared to the reference drug cisplatin. The rational design of conventional platinum analogues and the re-evaluation of the empirically derived "structure- activity" relationships allowed for the synthesis of platinum complexes with great diversity in structural characteristics, biochemical stability and antitumor properties. METHODS: The new compounds have been studied by elemental analyses, IR, NMR and mass spectral analyses. The structures of the organic compound and one of the new mixed/ammine Pt(II) complexes were studied by X-ray diffraction analysis. The cytotoxic effects of the compounds were studied vs. the referent antineoplastic agent cisplatin against four human tumour cell lines using the standard MTT-dye reduction assay for cell viability. The most promising complex 3 was investigated for acute toxicity in male and female H-albino-mice models. RESULTS: A new organic compound (5-methyl-5-(2-thiomethyl)ethyl hydantoin) L bearing both S- and Ncoordinating sites and three novel platinum complexes, 1, 2 and 3 were synthesized and studied. Spectral and structural characterization concluded monodentate S-driven coordination of the ligand L to the metal center in complexes 1 and 2, whereas the same was acted as a bidentate N,S-chelator in complex 3. Ligand L crystallizes in the tetragonal space group I41/a (No 88) with one molecule per asymmetric unit. While complex 3 crystallizes in the monoclinic space group P21/c (No 14) with one molecule per asymmetric unit. In the same complex 3, the platinum ion coordinates an L ligand, a chloride ion and an ammonia molecule. In the in vitro experiments, the tested L and complexes 1 and 2 exhibited negligible cytotoxic activity in all tumor models. Accordingly, complex 3 is twice as potent as cisplatin in the HT-29 cells and is at least as active as cisplatin on the MDA-MB-231 breast cancer cell line. In the in vivo toxicity estimation of complex 3 no signs of common toxicity were observed. CONCLUSION: The Pt(II)-bidentate complex 3 exhibited significant cytotoxic potential equaling or surpassing that of the reference drug cisplatin in all the tested tumor models. Negligible anticancer activity on the screened tumor types has been shown by the ligand L and its Pt(II) and Pt(IV) complexes 1 and 2, respectively. Our study on the acute toxicity of the most active complex 3 proved it to be non-toxic in mice models.

Oxidative Response and Micronucleus Centromere Assay in HEp-2 Cells Exposed to Fungicide Iprodione.

The fungicide agents are a key component in the fruits and vegetables production. The Iprodione residues are one of the pesticide more frequently found in food products. The available data about the cytotoxicity of iprodione and its metabolites are scarce and do not allow characterization of its genotoxic potential and define the risk assessment.The human larynx epidermoid carcinoma cell line (HEp-2) has been shown to be sensitive to the toxic effects of xenobiotics of different origin and have been often used in citotoxicity and genotoxicity studies. The purpose of this paper is to evaluate the induction of genotoxicity and the role of oxidative stress in HEp-2cell line by exposure to the IP. The MTT test for viability resulted in CL50 85.86 (77.05-95.68) µg/mL of Iprodione. On the basis of this result, we proceeded to expose the cells to the sublethal concentrations (below the CL50) during 24 h to analyze the mitotic index and nuclear division index in order to determine the subcytotoxic concentrations of IP which the genotoxicity was evaluated. The subcytotoxic concentrations of 7, 17, and 25 µg/mL IP induced aneugenic effects as micronuclei centromere positive whereas 17 µg/mL was a threshold for centromere negative micronuclei induction in HEp-2 cells. The abnormal mitosis was induced for exposition of Hep-2 cells to the three concentrations. According to the result obtained, citotoxicity and genotoxicity oxidative stress studies were performed in 1.5, 7.0, and 25 µg/mL of IP. The results showed that the GSH intracellular content, the SOD activity and the levels of oxidative damage of the proteins were affected lead to redox imbalance. The decreased in the SOD activity and protein oxidation were in according to the result obtained to genotoxicity, suggesting that different biological targets could be affected.

Formaldehyde Release From Personal Care Products: Chromotropic Acid Method Analysis.

BACKGROUND: Preservatives such as formaldehyde and formaldehyde releasers (F/FRs) are found in personal care products. Studies from Europe and Israel have indicated that products with undeclared F/FRs on product labels may have detectable levels of formaldehyde. OBJECTIVE: The aim of the study was to determine the presence of formaldehyde in samples of US personal care products. METHODS: Fifty-four baby and adult products were tested with the chromotropic acid method. A blinded investigator graded the color change as mild, moderate, or strong. RESULTS: All 8 products declaring F/FRs resulted in a deep purple color change, indicating a strong reaction. Of the 46 products with undeclared F/FRs, 4 (8.6%) were found to release formaldehyde. All 4 resulted in a light purple color change, indicating a mild reaction. CONCLUSIONS: Overall, 4 of 54 products (7.4%) had label information, which did not match chromotropic acid method testing results. Clinicians and formaldehyde-allergic individuals should be aware of the limitations of product ingredient labeling in managing allergic contact dermatitis to formaldehyde.

Identification and Profiling of Hydantoins-A Novel Class of Potent Antimycobacterial DprE1 Inhibitors.

Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-ß-d-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.