Occupational exposure to airborne mercury during gold mining operations near El Callao, Venezuela

Objective: The National Institute for Occupational Safety and Health (NIOSH) recently conducted a cross–sectional study during gold mining operations near El Callao, Venezuela. The purpose of the study was to assess mercury exposures and mercury-related microdamage to the kidneys. The study consisted of concurrent occupational hygiene and biological monitoring, and an examination of the processing techniques employed at the different mining facilities. Mercury was used in these facilities to remove gold by forming a mercury-gold amalgam. The gold was purified either by heating the amalgam in the open with a propane torch or by using a small retort. Methods: Thirty-eight workers participated in this study. Some participants were employed by a large mining company, while others were considered “informal miners” (self-employed). Mercury exposure was monitored by sampling air from the workers' breathing zones. These full-shift air samples were used to calculate time-weighted average (TWA) mercury exposure concentrations. A questionnaire was administered and a spot urine sample was collected. Each urine sample was analyzed for mercury, creatinine, and N-acetyl-ß-d-glucosaminidase (NAG). Results: The range for the 8-h TWA airborne mercury exposure concentrations was 0.1 to 6,315?μg/m³, with a mean of 183?μg/m³. Twenty percent of the TWA airborne mercury exposure measurements were above the NIOSH recommended exposure limit (REL) of 50?μg/m³, and 26% exceeded the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) of 25?μg/m³. The mean urine mercury concentration was 101?μg/g creatinine (μg/g-Cr), and the data ranged from 2.5 to 912?μg/g-Cr. Forty–two percent of the study participants had urine mercury concentrations that exceeded the ACGIH biological exposure index (BEI) of 35?μg/g-Cr. Urinary NAG excretion is considered a biological marker of preclinical, nonspecific microdamage to the kidney's proximal tubule cells. The mean urine NAG concentration was 3.6 International Units/g-Cr (IU/g-Cr) with a range of 0.5 to 11.5?IU/g-Cr. Three workers had urine NAG levels in excess of the reference values. Correlation analyses found statistically significant correlations between airborne mercury exposure and urine mercury level (P=0.01), and between urine mercury level and urine NAG excretion (P=0.01). In addition, the airborne mercury exposure data and urine mercury data were segregated by job tasks. A Wilcoxon rank sum test revealed significant correlations between tasks and mercury exposure (P=0.03), and between tasks and urine mercury level (P=0.02). Conclusions: The tasks with the highest mean airborne mercury exposures were “burning the mercury-gold amalgam” and “gold refining/smelting”. Recommendations were provided for improving the retort design to better contain mercury, for ventilation in the gold shops, and for medical surveillance and educational programs.     

Synthesis of new chalcone derivatives bearing 2,4-thiazolidinedione and benzoic acid moieties as potential anti-bacterial agents

A series of chalcone derivatives bearing the 2,4-thiazolidinedione and benzoic acid moieties (8a-s) were synthesized, characterized, and evaluated for their anti-bacterial activity. Among the tested compounds, the most effective were 8a, 8h, 8k, 8n and 8q with MIC value in the range of 0.5-4 μg/mL against six Gram-positive bacteria (including multidrug-resistant clinical isolates). None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 and E. coli 1682 at 64 μg/mL.     

Synthesis, evaluation against Leishmania amazonensis and cytotoxicity assays in macrophages of sixteen new congeners Morita-Baylis-Hillman adducts

We report the design, synthesis, in vitro evaluation against Leishmania amazonensis (IC₅₀), cytotoxicity assays in macrophages (CC₅₀), and selectivity index (SICC₅₀/IC₅₀) of sixteen new congeners aromatic Morita-Baylis-Hillman adducts 1-16. The 1-16 were prepared in good to excellent yields (58%-97%) from the “one pot” Morita-Baylis-Hillman Reaction between the aldehydes 29-36 and the acrylates 27 or 28 under DABCO as promoter. The MBHA 2-[Hydroxy(2-nitrophenyl)propyl] propanoate (1, IC₅₀ = 7.52 μg/mL or 28.38 μM; CC₅₀ = 35.77 μg/mL or 134.98 μM; SI = 4.75) and 2-[Hydroxy(2-nitrophenyl)hydroxyethyl] propanoate (9, IC₅₀ = 5.48 μg/mL or 20.52 μM; CC₅₀ = 29.81 μg/mL or 111.64c μM and, SI = 5.43) were the most effective and safe evaluated compounds.     

Synthesis, antimicrobial, antioxidant, anti-hemolytic and cytotoxic evaluation of new imidazole-based heterocycles

In the present work, 1-(5-methyl-2-phenyl-1H-imidazol-4-yl)ethanone 1 was prepared and used as a precursor for the synthesis of new thiazole, arylidiene and coumarin derivatives. The antimicrobial, antioxidant, anti-hemolytic, and cytotoxic activities of new compounds have been screened. Compound 12 showed an excellent antibacterial activity for all the tested bacteria with minimal inhibitory concentration (MIC) ranged between 21.9 and 43.8 μg/mL. While, compounds 2, 8 and 10a were the best antioxidant reagents using the DPPH method. Compounds 6a and 10b proved to exhibit potent antioxidative activity as reflected in the ability to inhibit lipid per-oxidation in rat brain and kidney homogenates and rate erythrocyte hemolysis. Compounds 6a proved to have the highest cytotoxic activity (81.9%) followed by 2, 6c, 7b and 12 using in vitro Ehrlich ascites assay. The details synthetic methods, spectroscopic data and biological results are recorded.     

Study on the cytochrome P-450- and glutathione-dependent biotransformation of trichloroethylene in humans

Objectives: To investigate in humans the contribution of the cytochrome P-450- and glutathione-dependent biotransformation of trichloroethylene (TRI) under controlled repeated exposure in volunteers, and under occupational conditions. Methods: Volunteers were exposed to TRI, using repeated 15?min exposures at 50 and 100?ppm. This exposure schedule resulted in internal doses of 1.30 and 2.40?mmol of TRI respectively. Urine samples were collected for a minimum of 45?h. Urine samples were also collected from occupationally exposed workers. The samples were analysed for the known human metabolites of TRI, trichloroethanol (TCE), trichloroacetic acid (TCA) and both regio-isomeric forms of the mercapturic acid N-acetyl-S-(dichlorovinyl)-l-cysteine (DCV-NAC), and for (dichlorovinyl)-l-cysteine (DCVC). In order to further elucidate the metabolism of TRI in humans, we analysed samples for dichloroacetic acid and for the proposed break-down products of 1,2 and 2,2-dichlorovinyl-L-cysteine after deamination: the S-conjugates of 3-mercaptolactic acid, 3-mercaptopyruvic acid and 2-mercaptoacetic acid. Results: None of the glutathione metabolites was found in urine of volunteers. In workers occupationally exposed to TRI at levels between 0.4 and 21?ppm [8-h time-weighted average (TWA)], levels of DCV-NAC in urine samples collected at the end of the 4th working day and also next morning were below detection limit (0.04?μmol/l). This confirms the findings of Bernauer et?al. (1996) that these metabolites are excreted at very low levels in humans. Urinary levels of DCVC and six postulated metabolites of dichlorovinyl-S-cysteine conjugates via deamination were also below 0.04?μmol/l, indicating that at most 0.05% of the dose is excreted in the form of these metabolites. These data further strengthen the argument for a very low activity of glutathione-mediated metabolism for chronically exposed workers. Conclusions: This study gives additional data which indicate that glutathione-mediated metabolism is of minor importance in humans exposed to TRI. In spite of indications to the contrary, significant metabolism of the cysteine conjugate via ß-lyase, which could result in a toxic metabolite, cannot be ruled out completely.     

Synthesis and in vitro anti-tumor activity of new oxadiazole thioglycosides

A facile, convenient and high yielding synthesis of novel thioglycosides incorporating 1,3,4-oxadiazole, triazole and or triazine moieties from readily available starting materials has been described. The key step of this protocol is the formation of 3-isobutyl-1-phenyl-1H-pyrazole-4-carbaldehyde (3) via condensation between methyl iso-butyl ketone and phenylhydrazine followed by application of Vilsmeier-Haack reaction. 3 was converted either to 1,3,4-oxadiazole derivative or condensed with O-aminothiols to give the bases 8, 19 and 20 in good yields, respectively. The aglycons 8, 19, and 20 were coupled with different activated halosugars in the presence of basic medium. Pharmacological evaluation of compounds 8, 14, 16 and 22 in vitro against 2-cell lines MCF-7 (breast) and HEPG2 (liver) revealed them to possess high anti-tumor activities with IC₅₀ values ranging from 2.67-20.25 (μg/mL) for breast cell line (MCF-7) and 4.62-43.6 (μg/mL) for liver cell line (HEPG2). None of the tested compounds exhibited any toxicity in doses up to 500 mg kg⁻¹ of the animal body weight.     

Synthesis, antimicrobial activity and structure-activity relationship study of N,N-dibenzyl-cyclohexane-1,2-diamine derivatives

We report herein synthesis and antimicrobial activity of a series of N,N-dibenzyl-cyclohexane-1,2-diamine derivatives. In order to study the structure-activity relationship of substituted dibenzyl-cyclohexane-1,2-diamine derivatives, 44 structurally diverse compounds were synthesized and tested against Gram-positive and Gram-negative bacterial strains. Among them, compounds 17-20, 26, 37, 38 were found to be more active than tetracycline with MIC value ranging 0.0005-0.032 μg/mL and no hemolysis upto 1024 μg/mL in mammalian erythrocytes was observed. Some of the compounds have also shown very promising antifungal activity against Candida albicans, Candida glabrata and Geotrichum candidium.     

SPF32629A and SPF32629B: enantioselective synthesis, determination of absolute configuration, cytotoxicity and antibacterial evaluation

We report herein an efficient enantioselective synthesis of SPF32629A and SPF32629B through one-pot enantioselective reduction and protecting-group-free regioselective O-acylation strategy. The absolute configuration of the enantiomerically pure isomers was established by Mosher ester analysis. The inhibitory potencies of the synthesized compounds were assayed in vitro against a panel of microorganisms and against A549 human lung adenocarcinoma cell line. Compounds 2, 11 and 12 displayed moderate to potent antibacterial activity against all the tested strains and compounds 7, 8, 2, 11 and 12 exhibited significant cytotoxicity in a dose-dependent manner with an IC₅₀ values ranging from 2.92 to 4.14 μg/ml and 8-11 μM.     

Mycobacterium tuberculosis and cholinesterase inhibitors from Voacanga globosa

Globospiramine (1), a new spirobisindole alkaloid possessing an Aspidosperma-Aspidosperma skeleton, together with deoxyvobtusine (2), deoxyvobtusine lactone (3), vobtusine lactone (4) and lupeol (5), were isolated and identified from Voacanga globosa through a bioassay-guided purification. The gross structure and absolute stereochemistry of 1 were established by circular dichroism spectroscopy, HR-MS and unambiguous NMR spectroscopic experiments. In addition, a new biogenetic pathway for the formation of the spiro-Aspidosperma-Aspidosperma skeleton is proposed. Alkaloid 1 showed potent antituberculosis activity against Mycobacterium tuberculosis H₃₇Rv as evidenced in microplate Alamar blue assay (MIC = 4 μg/mL) and low-oxygen recovery assay (LORA (MIC = 5.2 μg/mL). The bisindole alkaloids also exhibited promising activity against acetylcholinesterase and, especially butyrylcholinesterase, with deoxyvobtusine (2) (IC₅₀ = 6.2 μM) as the most strongly inhibiting compound. This study extends the variety of alkaloid structural platforms which exhibit antimycobacterial and anticholinesterase activity.     

Does the choice of neighbourhood supermarket access measure influence associations with individual-level fruit and vegetable consumption? A case study from Glasgow

Background

Anopheles albimanus is among the most important vectors of human malaria in Mesoamerica and the Caribbean Basin (M-C). Here, we use topographic data and 1950?C2000 climate (near present), and future climate (2080) layers obtained from general circulation models (GCMs) to project the probability of the species?? presence, p(s), using the species distribution model MaxEnt.

Results

The projected near-present distribution parameterized with 314 presence points related well to the known geographic distribution in the study region. Different model experiments suggest that the range of An. albimanus based on near-present climate surfaces covered at least 1.27 million km² in the M-C, although 2080 range was projected to decrease to 1.19 million km². Modeled p(s) was generally highest in Mesoamerica where many of the original specimens were collected. MaxEnt projected near-present maximum elevation at 1,937?m whereas 2080 maximum elevation was projected at 2,118?m. 2080 climate scenarios generally showed increased p(s) in Mesoamerica, although results varied for northern South America and no major range expansion into the mid-latitudes was projected by 2080.

Conclusions

MaxEnt experiments with near present and future climate data suggest that An. albimanus is likely to invade high-altitude (>2,000?m) areas by 2080 and therefore place many more people at risk of malaria in the M-C region even though latitudinal range expansion may be limited.     

Excessive iodine intake in schoolchildren

Purpose

Inadequate iodine intake may result in iodine deficiency disorders (IDD). Thus, for more than 50?years, policies for the regulation of salt fortification with iodine have existed in Brazil. In 2003, a study on 6–14-year-old schoolchildren from regions of the state of S?o Paulo showed a median urinary iodine concentration of 360?μg/L. The objective of the present study was to assess the iodine nutrition status among schoolchildren.

Methods

The study was conducted on 828 schoolchildren aged 4–13?years from eight schools in the interior of the state of S?o Paulo. A casual urine sample was collected from each volunteer for iodine determination by the adapted method of Sandell-Kalthoff.

Results

Only 1.9% (n?=?16) of the children evaluated had low values of urinary iodine (<100?μg/L), while 24.6% had urinary iodine excretion values between 200 and 300?μg/L, and 67.1% had values above >300?μg/L.

Conclusions

The results show that the iodine nutritional status of the schoolchildren studied is characterized by a high urinary iodine excretion, which might reveal an increase in iodine consumption by this population.     

Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources,

Background

Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves.

Objectives

To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors.

Methods

Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and cold vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated.

Results

The median kidney concentrations were 12.9 μg/g (wet weight) for cadmium, 0.21 μg/g for mercury, and 0.08 μg/g for lead. Kidney Cd increased by 3.9 μg/g for a 10 year increase in age, and by 3.7 μg/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5 μg/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed.

Conclusions

In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.     

Assessing surrogacy of data sources for institutional comparisons

Can administrative claims data, Z, serve as a surrogate for better clinical data, X, when assessing institutional performance? We consider an analysis of I hospitals, each of which involves an adjusted outcome. In the i ^th hospital, we denote the true association between the outcome and the risk factors using one data source by θ _i (X), the true association between the outcome and the risk factors using the other data source by γ _i (Z), and assume we have estimates of each available. Within hospital i, the estimated association parameters are jointly normally distributed such that conditional on γ _i (Z), a simple linear relationship exists between θ _i (X) and γ _i (Z). Methods are illustrated using mortality rates for 181,032 elderly US heart attack patients treated at 4322 hospitals. We find a strong linear relationship between the hospital standardized mortality rates adjusted by risk factors found in administrative claims data and rates adjusted by risk factors found in medical charts (posterior mean [95% interval] for slope: 0.997 [0.965,1.028]). However, the absolute and relative differences between the two sets of rates increase as hospital volume increases. For typically-sized standard deviations of claims-based rates, there is reasonable certainty of quality problems when the hospital’s claims-based rate is 0.72 times or smaller than the national mean or 1.45 times or greater than the national mean. Fewer hospitals are classified as either low-mortality or high-mortality hospitals when using claims-based estimates compared to chart-based estimates.     

Synthesis and effects of some novel tetrahydronaphthalene derivatives on proliferation and nitric oxide production in lipopolysaccharide activated Raw 264.7 macrophages

In this study, novel N-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-yl)-carboxamide (6-15) and 5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide (16-32) derivatives were synthesized and their in vitro effects at 5 μM and 50 μM concentrations on proliferation and nitric oxide (NO) production in lipopolysaccharide (LPS) activated RAW 264.7 macrophage cells were determined. Compounds 12, 17, 24 and 26 were found to decrease nitrite levels in a dose-dependent manner in LPS-activated cells. At the tested concentrations, these compounds did not exhibit cytotoxic effects. Interestingly, compound 27 which contains nitroxide free radical was the most active compound in this series showing 59.2% nitrite inhibition in LPS-activated macrophage cells.     

Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives

A series of novel 1,2,4-triazole derivatives with a 4-(4-substitutedphenyl) piperazine side chain were designed and synthesized based on the structure of lanosterol 14α-demethylase (CYP51). Their antifungal activities against eight human pathogenic fungi were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds were found to be more potent against Candida albicans than control drug fluconazole. Noticeably, the MIC₈₀ value of compounds 6,7,9,14 and 29 is 16 times lower than that of voriconazole against C. albicans. The activities of compounds 7 and 21 against Cryptococcus neoformans in vitro are comparable to that of voriconazole with a MIC₈₀ value of 0.0156 μg/mL. Moreover, the molecular model for the binding between compound 7 and the active site of CACYP51 was provided based on the computational docking results.     

New fluorine-containing hydrazones active against MDR-tuberculosis

Several new fluorine-containing hydrazones were synthesized and screened for their in vitro antimycobacterial activity. Nine of these derivatives have shown a remarkable activity against MDR-TB strain with MIC 0.5 μg/mL and high value of selectivity index (SI). Compound 3h with the highest SI (1268.58) was used for stability evaluation with putative metabolites (ciprofloxacin and formylciprofloxacin) detection. Compound 3h was stable at pH 7.4 of aqueous buffer and rat plasma, in acidic buffers (at pH 3 and 5) slow decomposition was observed. Interestingly, no formylciprofloxacin was detected in the solution, and only slightly increased concentration of ciprofloxacin was observed instead. Trifluoromethyl hydrazones 3f and 3g exhibited the best activity also against two strains of Mycobacterium kansasii (MIC 1-4 μmol/L). All evaluated compounds were found to be non-cytotoxic.     

Synthesis and in vitro antibacterial activity of a series of novel gatifloxacin derivatives

A series of novel gatifloxacin (GTFX) derivatives were designed, synthesized and characterized by ¹H NMR, ¹³C NMR, MS and HRMS. These derivatives were evaluated for in vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Our results reveal that most of the target compounds show good potency in inhibiting the growth of Staphylococcus aureus including MRSA and Staphylococcus epidermidis including MRSE. Compounds 8, 14 and 20 have useful activity against all of the tested Gram-positive and Gram-negative strains (MICs: 0.06-4 μg/mL). In particular, 20 possessing a broad antimicrobial spectrum (MICs: 0.06-1 μg/mL) was found to be 2-32-folds more potent than the reference drug levofloxacin and parent GTFX against Pseudomonas aeruginosa.     

Design, synthesis and docking studies of quinoline-oxazolidinone hybrid molecules and their antitubercular properties

New series of quinoline-oxazolidinone hybrid molecules were synthesized based on the preliminary docking studies. All the newly synthesized compounds were characterized by spectral analyses. The newly synthesized compounds were screened for their antimycobacterial properties based on the promising preliminary antibacterial screening results. Amongst tested compounds, compounds 8a, 8j and 13a were active at 0.65 μg/mL against Mycobacterium tuberculosis H₃₇Rv strain. The mode of action of these active compounds was carried out by docking of receptor enoyl-ACP reductase with newly synthesized candidate ligands 8a, 8j and 13a. These compounds exhibited well established bonds with one or more amino acids in the receptor active pocket. From the docking studies, compound 8j was considered to be the best inhibitor.     

The new 5- or 6-azapyrimidine and cyanuric acid derivatives of l-ascorbic acid bearing the free C-5 hydroxy or C-4 amino group at the ethylenic spacer: CD-spectral absolute configuration determination and biological activity evaluations

We report on the synthesis of the novel types of cytosine and 5-azacytosine (1-9), uracil and 6-azauracil (13-18) and cyanuric acid (19-22) derivatives of l-ascorbic acid, and on their cytostatic activity evaluation in human malignant tumour cell lines vs. their cytotoxic effects on human normal fibroblasts (WI38). The CD spectra analysis revealed that cytosine (5 and 6), uracil (14-16), 6-azauracil (17) and cyanuric acid (21) derivatives of l-ascorbic acid bearing free amino group at ethylenic spacer existed as a racemic mixture of enantiomers, whereas L-ascorbic derivatives containing the C-5 substituted hydroxy group at the ethylenic spacer were obtained in (4R, 5S) enantiomeric form. The stereochemistry of 6-azauracil derivative of l-ascorbic acid (13) was confirmed by X-ray crystal structure analysis. The molecules are self-assembled by one N-H?O hydrogen bond, two C-H?O hydrogen bonds and two C-H?π interactions into three-dimensional framework. Cytostatic activity evaluation indicated that compounds did not show distinctive antiproliferative effects on tested cell line panel. However, the cytosine derivative of l-ascorbic acid (1) containing the C4-C5 double bond conjugated with the lactone moiety produced rather marked growth inhibitory effect on hepatocellular carcinoma (HepG2), metastatic breast epithelial carcinoma (MCF-7) and cervical carcinoma (HeLa) cell lines at micromolar concentrations, but also exerted strong cytostatic effect on WI38. 5-Azacytosine derivative of l-ascorbic acid (2) with a double bond at the C4-C5 conjugated with the lactone moiety displayed potent antitumour activity against tested tumour cell lines with meanIC₅₀ values ranging from 0.92 to 5.91 μM. However, this compound also exhibited pronounced cytotoxicity towards WI38. Flow cytometric analysis of the cell cycle revealed that compound 2 triggers S phase arrest, which clearly demonstrates its interference with DNA replication, a key event of cell proliferation. Marked anticancer efficacy of compound 2 supports further in vivo investigation into its possible clinical utility.     

Synthesis and antiproliferative activity of novel symmetrical alkylthio- and alkylseleno-imidocarbamates

The study described here concerns the synthesis of a series of thirty new symmetrically substituted imidothiocarbamate and imidoselenocarbamate derivatives and their evaluation for antitumoral activity in vitro against a panel of five human tumor cell lines: breast adenocarcinoma (MCF-7), colon carcinoma (HT-29), lymphocytic leukemia (K-562), hepatocarcinoma (Hep-G2), prostate cancer (PC-3) and one non-malignant mammary gland-derived cell line (MCF-10A). The GI₅₀ values for eighteen of the compounds were below 10 μM in at least one cell line. Two cancer cells (MCF-7 and HT-29) proved to be the most sensitive to five compounds (1b, 2b, 3b, 4b and 5b), with growth inhibition in the nanomolar range, and compounds 1b, 3b, 7b, 8b and 9b gave values of less than 1 μM. In addition, all of the aforementioned compounds exhibited lower GI₅₀ values than some of the standard chemotherapeutic drugs used as references. The results also reveal that the nature of the aliphatic chain (methyl is better than benzyl) at the selenium position and the nature of the heteroatom (Se better than S) have a marked influence on the antiproliferative activity of the compounds. These findings reinforce our earlier hypothesis concerning the determinant role of the selenomethyl group as a scaffold for the biological activity of this type of compound. Considering both the cytotoxic parameters and the selectivity index (which was compared in MCF-7 and MCF-10A cells), compounds 2b and 8b (with a selenomethyl moiety) displayed the best profiles, with GI₅₀ values ranging from 0.34 nM to 6.07 μM in the five cell lines tested.Therefore, compounds 2b and 8b were evaluated by flow cytometric analysis for their effects on cell cycle distribution and apoptosis in MCF-7 cells. 2b was the most active, with an apoptogenic effect similar to camptothecin, which was used as a positive control. Both of them provoked cell cycle arrest leading to the accumulation of cells in either G₂/M and S phase.These two compounds can therefore be considered as the most promising candidates for the development of novel generations of antitumor agents.