Organotin(IV) complexes of tridentate (ONO) hydrazone ligands: synthesis, spectral characterization, antituberculosis, antimicrobial, anti-inflammatory, molecular docking and cytotoxicity studies.

Infectious diseases have a significant impact in the historical trajectory of humanity, exerting profound influence on societies, driving advancements in medical science, and significantly impacting individuals on a worldwide scale. Consequently, this research endeavours to identify potent agents combatting tuberculosis, inflammation, and microbial deformities. The investigation focuses on hydrazones (1,2) endowed eight organotin(IV) complexes, where hydrazones were derived from 2-acetyl-1H-indene-1,3(2H)-dione and 2-phenoxypropanehydrazide/2-(2,4-dichlorophenoxy)propanehydrazide. All compounds underwent thorough characterization utilizing a variety of spectral and analytical techniques including, multinuclear NMR, FT-IR, HRMS, UV-Vis, SEM-EDAX, TGA, XRD, molar conductance measurements, establishing the pentacoordinated environment around tin(IV) ion with tridentate (ONO) mode of chelation of hydrazones. Powder XRD revealed the ligand's crystalline and complexes' semi-crystalline nature, while thermal analysis indicated two-step decomposition leaving tin oxide residue. In vitro evaluations utilize microplate alamar blue assay for assessing anti-tuberculosis activity, serial dilution technique for antimicrobial efficacy, and bovine serum albumin method for evaluating anti-inflammatory properties. The complexes exhibited higher biological activities than their respective ligands and the activity of the complexes follow the order: Ph2SnL1-2 > Bu2SnL1-2 > Et2SnL1-2 > Me2SnL1-2. Among them, phenyl complex (10) [Ph2SnL2] displays superior efficacy against TB dysfunction (MIC: 0.0180 ± 0.009 µmol/mL) and also demonstrates exceptional potency in combating inflammation (IC50: 7.27 ± 0.04 µM), and microbial (MIC: 0.0045 µmol/mL) infections, comparable to standard drugs. Additionally, cytotoxicity testing against vero cell line revealed decreased toxicity at lower concentrations, and attenuated by chelation. Phenyl complex (10) [Ph2SnL2] shows promising cytotoxicity at 3.12 µg/mL (19.29 ± 0.09%). Further, The diphenyltin(IV) complex (10), identified as the most effective against TB, shows stronger binding to key 3PTY protein residues (- 42.2 kJ/mol) compared to ligand (2) (- 33.4 kJ/mol), correlating with its superior anti-tuberculosis potency in biological assays. This comprehensive approach aims to actively contribute to ongoing initiatives addressing infectious diseases, thereby advancing global health and overall well-being.

Organotin exposure and DNA methylation in non-syndromic cleft lip and palate: Integrating findings from case-control studies and animal experiments.

Human exposure to organotin is common but little is known about the adverse pregnancy outcomes. This study aimed to explore the association between organotin exposure and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and to explore the underlying mechanism. Placental samples (109 NSCL/P cases and 128 controls) were analyzed for 8 organotin concentrations, and subsequent animal experiments were conducted by administering tributyltin (TBT) during critical developmental periods. DNA methylation BeadChip analysis (12 NSCL/P and 12 controls), bisulfite Sequencing analysis (3 NSCL/P and 3 controls mice), and RNA sequencing were performed to explore epigenetic mechanisms. Logistic regression, LASSO regression, support vector machine, random forest, and mediation effect analysis were utilized to identify key genes related to TBT and NSCL/P. Only tributyltin met the detection criteria for further analysis among 8 compounds. The median levels of TBT in cases (8.93 ng/g) were statistically significantly higher than those in controls (5.33 ng/g). Excessive TBT exposure in maternal placenta was associated with an increased risk of NSCL/P (OR = 6.44, 95 % CI, 2.91-14.25) in humans, showing a dose-response relationship (p for trend <0.05). 288 differentially methylated CpG sites in 129 genes were identified between cases and controls. Tributyltin was associated with FGFR2 and SCD hypomethylation, which were identified as potential key genes associated with NSCL/P. Mediation analysis suggested that DNA methylation of FGFR2 and SCD may mediate the impact of TBT on NSCL/P occurrence. TBT exposure during the critical period in mice (GD8.5-GD15.5) can induce progeny NSCL/P. Altered FGFR2 and SCD hypomethylation and gene expression observed in response to TBT exposure in fetal mice. Excessive TBT exposure was associated with increased risks of human NSCL/P. TBT exposure can induce NSCL/P in fetal mice. FGFR2 and SCD were implicated in NSCL/P pathogenesis, potentially mediated by DNA methylation alterations.

Imposex incidence in gastropod species from the Colombian Caribbean Coast reveals continued and widespread tributyltin contamination after its global ban.

Organotin compounds (OTCs), such as tributyltin (TBT) and triphenyltin (TPhT), are released in aquatic environments from antifouling coatings and can cause imposex, an abnormal condition where female snails develop male sexual characteristics. This study investigates temporal variations in imposex incidence along the Colombian Caribbean coast following the 2008 global ban on TBT-based antifouling paints. Over a 12-year period, we assessed imposex in 1,384 adults snails from six species (58% female and 42% male) during 2012, 2016, and 2023. In 2012, just four years after the ban, imposex incidence in some sites reached 100% in the neogastropods Purpura patula, Stramonita haemastoma, Stramonita rustica, and Thais deltoideia. In 2016, imposex in some sites reached 81% for the mesogastropod Strombus pugilis and 39% for the neogastropod Melongena melongena. By 2023, imposex decreased for the first four neogastropods, persisted for S. pugilis, and increased for M. melongena only in Cartagena Bay and the Tolú marina. These findings indicate a general decline in imposex over time, aligning with the ban, but also suggest potential new sources of contamination as imposex rates increased in some previously unaffected areas.

Organotin(IV) complexes derived from 2,6-diacetylpyridine bis(2-hydroxybenzoylhydrazone) as prospective anti-proliferative agents: Synthesis, characterization, structures and in vitro anticancer activity.

Six organotin(IV) complexes, viz., [Me2Sn(L)] (1), [n-Bu2Sn(L)] (2), [n-Oct2Sn(L)] (3), [Bz2Sn(L)]·0.5C7H8 (4), [n-BuSn(L)Cl] (5), and [PhSn(L)Cl] (6), were synthesized using a 2,6-diacetylpyridine bis(2-hydroxybenzoylhydrazone), H2L. Compounds were characterized by Fourier transform infrared (FT-IR), High-resolution mass spectrometry (HRMS), and solutions Fourier transform nuclear magnetic resonance (FT-NMR) spectroscopies. The structures 1-6 were established by single-crystal X-ray diffraction (SC-XRD) analysis. Diffraction results evidenced that complexes 1-6 were seven-coordinated mononuclear species with the equatorial plane comprising the pentagonal N3O2 chelate ring of the doubly deprotonated L and two axial ligands, either R (R = Me, n-Bu, n-Oct, Bz) or R (n-Bu or Ph) and Cl ligands. Additionally, the photophysical properties were examined due to the enhanced conjugation and rigidity of the molecules while thermogravimetric analysis was carried out to evaluate the thermal stabilities of compounds. The anti-proliferative activity of the complexes 1-6 was tested against prostate cancer cells (DU-145) and normal human embryonic kidney cells (HEK-293). Among the compounds, dibutyltin compound 2 exhibited increased anti-proliferative activity, with an IC50 value of 6.16 ± 1.56 µM. The investigation of its mechanism of action involves using AO/EB (acridine orange/ethidium bromide) and ROS (reactive oxygen species) generation assays. This likely detects apoptotic morphological alterations in the nucleus of the cells, with ROS generation ultimately leading to apoptosis and cell death. The superior activity of 2 may be attributed to the C···H contacts and respective higher de outside and di inside distances from the Hirshfeld surface. Thus, these compounds could be a promising alternative to classical chemotherapy agents.

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Medical polyurethanes have emerged as a leading choice for biomedical applications owing to their exceptional biocompatibility and good physical and mechanical properties. Catalysts play a crucial role as additives in the synthesis of medical polyurethanes, enhancing synthesis efficiency and material properties. However, the catalysts used may affect the biocompatibility of polyurethanes and pose potential harm to human health. This review encapsulates the latest findings regarding the catalysts employed in the synthesis of medical polyurethane materials and their biotoxicity. Initially, we reviewed the prevalent types of catalysts used in the synthesis of medical polyurethane materials and described their distinctive characteristics. Subsequently, our focus shifted to exploring the potential biotoxicity associated with these catalysts. Finally, we provided a forward-looking perspective and recommendations for the future trajectory of catalyst selection in the synthesis of medical polyurethane materials. By acquiring a more profound understanding of the properties and biotoxicity of catalysts used in the synthesis of medical polyurethane materials, and by uncovering existing issues and challenges, we can better guide the design of medical polyurethane materials. This, in turn, enables us to chart the course for future development and ultimately enhance the biocompatibility and safety profiles of medical polyurethane materials. Such advancements will promote the continued development and application of medical polyurethane materials in clinical settings.

Synthesis of organotin(IV) heterocycles containing a xanthenyl group by a Barbier approach via ultrasound activation: synthesis, crystal structure and Hirshfeld surface analysis.

A series of organotin heterocycles of general formula [{Me2C(C6H3CH2)2O}SnR2] [R = methyl (Me, 4), n-butyl (n-Bu, 5), benzyl (Bn, 6) and phenyl (Ph, 7)] was easily synthesized by a Barbier-type reaction assisted by the sonochemical activation of metallic magnesium. The 119Sn{1H} NMR data for all four compounds confirm the presence of a central Sn atom in a four-coordinated environment in solution. Single-crystal X-ray diffraction studies for 17,17-dimethyl-7,7-diphenyl-15-oxa-7-stannatetracyclo[11.3.1.05,16.09,14]heptadeca-1,3,5(16),9(14),10,12-hexaene, [Sn(C6H5)2(C17H16O)], 7, at 100 and 295 K confirmed the formation of a mononuclear eight-membered heterocycle, with a conformation depicted as boat-chair, resulting in a weak Sn...O interaction. The Sn and O atoms are surrounded by hydrophobic C-H bonds. A Hirshfeld surface analysis of 7 showed that the eight-membered heterocycles are linked by weak C-H...π, π-π and H...H noncovalent interactions. The pairwise interaction energies showed that the cohesion between the heterocycles are mainly due to dispersion forces.

Transcriptomic analysis reveals the endocrine toxicity of tributyltin and triphenyltin on the whelk Reishia clavigera and mechanisms of imposex formation.

Organotin compounds (OTs) are endocrine disruptors that induce imposex in hundreds of gastropods, but little is known about their underlying molecular mechanisms. This study aimed to investigate the endocrine toxicity and molecular responses to tributyltin (TBT) and triphenyltin (TPT) exposure in the whelk Reishia clavigera, which often serves as a biomonitor for OT contamination. Over a 120-day exposure to environmentally relevant concentrations of TBT (1000 ng L-1) and TPT (500 ng L-1), we observed a significant increase in penis length in both male and female whelks. Notably, TPT exhibited a stronger potency in inducing pseudo-penis development and female sterility, even at a half dose of TBT. Bioaccumulation analysis also revealed higher persistence and accumulation of TPT in whelk tissues compared to TBT. Differential expression analysis identified a substantial number of differentially expressed genes (DEGs), with TPT exposure eliciting more DEGs than TBT. Our results demonstrated that OTs induced xenobiotic metabolism and metabolic dysregulation in the digestive gland, impaired multiple cellular functions and triggered neurotoxicity in the nervous system, and disrupted lipid homeostasis and oxidative stress in the gonads. Furthermore, imposex was possibly associated with disturbances in retinoic acid metabolism, nuclear receptor signaling, and neuropeptide activity. When compared to TBT, TPT exhibited a more pronounced endocrine-disrupting effect, attributable to its higher bioaccumulation and substantial interruption of transcriptional regulation, OT detoxification, and biosynthesis of retinoic acids in R. clavigera. Our results, therefore, highlight the importance of considering the differences in bioaccumulation and molecular toxicity between TBT and TPT in future risk assessments of these contaminants. Overall, our study provided molecular insights into the toxicity and transcriptome profiles in R. clavigera exposed to TBT and TPT, shedding light on the endocrine-disrupting effects and reproductive impairment in female gastropods.

Synthesis and anti-tumor activities of three newly designed organotin(IV) carboxylates complexes.

Three distinctive end group-containing organotin (IV) carboxylates complexes (YDCOOSn, CLCOOSn and BZCOOSn) were designed and synthesized. Together with theoretical calculations, a thorough examination was carried out to investigate the photophysical properties of these compounds. The cytotoxicity of the synthesized compounds was tested using normal cell line GES-1 and was assessed against four cancer cell lines (A549, Hela, H1299 and HepG2). The outcomes of the experiments demonstrated that these complexes had superior selectivity than cisplatin towards cancerous cells, particularly in the A549 cell line. BZCOOSn was selected as a candidate compound for additional research because it exhibited the lowest IC50 value and the most impressive inducing effect on cell death and G2/M phase arrest. Increased caspase-3 and -9 enzyme activity, a decline in mitochondrial membrane potential (MMP), characteristic nuclear apoptotic morphology, and an accumulation of intracellular reactive oxygen species (ROS) were seen in A549 exposed to BZCOOSn. These findings demonstrated that BZCOOSn exhibited strong cytotoxicity by triggering cell death in A549 via the mitochondrial route. Furthermore, using the scratch wound healing assay, it was discovered that BZCOOSn reduced the migration of A549 cancerous cells. These data all pointed to BZCOOSn as a possible candidate for more research and development as a chemotherapeutic drug.

Diorganotin (IV) amino acid complexes as potential anticancer agents. Synthesis, structural characterization, and in vitro assays.

Nine new organotin (IV) derivatives from L-amino acids (l-lysine, L-ornithine, L-glutamic acid, and L-aspartic acid) were synthesized by one-pot ultrasound-assisted methodology. All compounds were characterized by ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared), LRMS (Low-Resolution Mass Spectrometry), and solution NMR (1H, 13C, 119Sn Nuclear Magnetic Resonance) spectroscopies. Complexes Bu2Sn(Lys) (1), Ph2Sn(Lys) (2), Bu2Sn(Orn) (3), and Ph2Sn (Glu-OMe) (6a) were crystallized, and the structures were established by single-crystal X-ray diffraction analysis. Diffraction results evidenced that complexes 1 to 3 were five-coordinated mononuclear species while the phenyl substituted derivative Ph2Sn (Glu-OMe) (6a) forms a polymeric network via Sn-O-Sn bridging whereby the tin atom is six-coordinated. In turn, 119Sn NMR results revealed that all tin complexes exist as mononuclear penta-coordinated species in solution. The tin derivatives were screened for ADME (Adsorption, Distribution, Metabolism, and Excretion) properties via the freely available tools SWISS ADME, and the results were analyzed hereafter. The antiproliferative activity of the complexes was tested against three human cancer cell lines: colorectal adenocarcinoma HT-29, breast adenocarcinoma MDA-MB-231, and chondrosarcoma SW-1353 using a non-tumoral cell line of human osteoblast as control, demonstrating selective inhibitory activities against cancer cells. Hence, these compounds could be a promising alternative to classical chemotherapy agents.

Design, synthesis and mechanistic studies of novel arylformylhydrazone butylphenyltin complexes as potential anticancer agents.

Many diorganotin complexes with various alkyl groups exhibit excellent in vitro anticancer activity. However, most diorganotin is the same alkyl group, and the asymmetric alkyl R group has been rarely reported. Hence, in this paper, twenty butylphenyl mixed dialkyltin arylformylhydrazone complexes have been synthesized by microwave "one-pot" reaction with arylformylhydrazine, substituted α-keto acid or its sodium salt and butylphenyltin dichloride. The crystal structures of nine complexes were determined, indicating that the complexes C1, C2, C11, C12, and C16 âˆ¼ C19 possessed a central symmetric structure of a dinuclear Sn2O2 tetrahedral ring; while the complex C9 is a trinuclear tin-oxygen cluster with a 6-membered ring encased in a 12-membered macrocyclic structure. The inhibiting activity of complexes was tested against the human cell lines NCI-H460, MCF-7, HepG2, Huh-7 and HL-7702. Complex C2 demonstrated the optimal inhibitory effect on HepG2 cells, with an IC50 value of 0.82 ± 0.03 µM. Cellular biology experiments revealed that complex C2 could induce apoptosis and G2/M phase cell cycle arrest in HepG2 and Huh-7 cells. The complex also caused the collapse of the mitochondrial membrane potential and increased intracellular reactive oxygen species in HepG2 and Huh-7 cells. Western blot analysis further clarified that complex C2 could induce cell apoptosis through the mitochondrial pathway along with the release of reactive oxygen species.

Bioaccumulation of organotin compounds in the marbled electric ray (Torpedo marmorata) in the northern Adriatic Sea.

Organotin compounds (OTC), tri-, di- and monobutyl tin, were determined in the tissues of marbled electric ray (Torpedo marmorata) in the Adriatic Sea. Marbled electric ray specimens were provided by local fishermen from three localities in the northern Adriatic: area close to the shipyard in Seca, the natural protected area Strunjan Nature Reserve and along the west Istrian coast. To assess the concentration of OTC in the environment, sediment samples were also analysed. After an adequate extraction of OTC from both matrices, their concentrations were determined by GC-ICP-MS. The results indicate that the accumulation of TBT (tributyltin) and DBT (dibutyltin) in the marbled electric ray is related to the possible pollution sources, since their total concentrations were significantly higher (p < 0.001) in the area close to the shipyard (up to 69 µg Sn kg-1, w.w.) in comparison to the other two areas less affected by direct pollution (up to 7 µg Sn kg-1, w.w.). TBT concentrations ranged from 2 to 42 µg Sn kg-1, w.w., DBT concentrations were in the range from 2 to 22 µg Sn kg-1, w.w., and MBT concentrations were mostly below the detection limit with the highest up to 4 µg Sn kg-1, w.w. The proportion of the three determined congener concentrations in sediment samples indicate a temporally older pollution with these compounds, with prevailing DBT and MBT concentrations up to 30 µg Sn kg-1, w.w., and much lower TBT concentrations up to 7 µg Sn kg-1, w.w. According to our results, marbled electric ray could be considered as an ideal bioindicator of environmental pollution due to its ecological characteristics.

The Development of Organotin(IV) N-Ethyl-N-Benzyldithiocarbamate Complexes: A Study on Their Synthesis, Characterization, and Cytocidal Effects on A549 Cell Line.

BACKGROUND: Organotin(IV) complexes of dithiocarbamate are vital in medicinal chemistry, exhibiting potential in targeting cancer cells due to their unique properties that enhance targeted delivery. This study aimed to synthesize and characterize organotin(IV) N-ethyl-N-benzyldithiocarbamate complexes (ONBDCs) and evaluate their cytotoxicity against A549 cells, which are commonly used as a model for human lung cancer research. METHODS: The two ONBDC derivatives - ONBDC 1 (dimethyltin(IV) N-ethyl-N-benzyldithiocarbamate) and ONBDC 2 (triphenyltin(IV) N-ethyl-N-benzyldithiocarbamate) - were synthesized via the reaction of tin(IV) chloride with N-ethylbenzylamine in the presence of carbon disulfide. A range of analytical techniques, including elemental analysis, IR spectroscopy, NMR spectroscopy, UV-Vis spectrometry, TGA/DTA analysis, and X-ray crystallography, was conducted to characterize these compounds comprehensively. The cytotoxic effects of ONBDCs against A549 cells were evaluated using MTT assay. RESULTS: Both compounds were synthesized and characterized successfully via elemental and spectroscopies analysis. MTT assay revealed that ONBDC 2 demonstrated remarkable cytotoxicity towards A549 cells, with an IC50 value of 0.52 µM. Additionally, ONBDC 2 displayed significantly higher cytotoxic activity against the A549 cell line when compared to the commercially available chemotherapeutic agent cisplatin (IC50: 32 µM). CONCLUSION: Thus, it was shown that ONBDC 2 could have important anticancer properties and should be further explored as a top contender for creating improved and specialized cancer treatments.

Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells.

A novel trimethyltin(IV) complex (Me3SnL), derived from 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoate ligand, has been synthesized and characterized by elemental microanalysis, UV/Vis spectrophotometry, FT-IR and multinuclear (1H, 13C and 119Sn) NMR spectroscopies. Furthermore, the structure of the ligand precursor HL was solved using SC-XRD (single-crystal X-ray diffraction). The prediction of UV/Vis and NMR spectra by quantum-chemical methods was performed and compared to experimental findings. The protein binding affinity of Me3SnL towards BSA was determined by spectrofluorometric titration and subsequent molecular docking simulations. Me3SnL has been evaluated for its in vitro anticancer activity against three human cell lines, MCF-7 (breast adenocarcinoma), A375 (melanoma) and HCT116 (colorectal carcinoma), and three mouse tumor cell lines, 4T1 (breast carcinoma), B16 (melanoma) and CT26 (colon carcinoma), using MTT and CV assays. The strong inhibition of A375 cell proliferation, ROS/RNS upregulation and robust lipid peroxidation lead to autophagic cell death upon treatment with Me3SnL.

Carbon-Sulfur Bond Cleavage in Methanesulfonate on Diorganotin Quinaldate Platform - Synthesis and Characterization of [(n-Bu2SnL)2SO4].

The synthesis of mixed ligand di-n-butyltin complexes, [(n-Bu2SnL1-3)2SO4], 2-4 (HL1-3=2-quinoline/ 1-isoquinoline/ 4-methoxy-2-quinoline carboxylic acid) has been realized by reacting n-Bu2Sn(OMe)OSO2Me, 1 a with the corresponding quinaldic acid under solvothermal conditions. The observed transformation of methane sulfonate to sulfate anion represents a rare example of C-S bond cleavage on the organotin scaffolds, n-Bu2Sn(L1-3)OSO2Me, which have been identified as en route intermediates by NMR and X-ray crystallography. Analogous reaction when extended with Me2Sn(OMe)OSO2Me, 1 b and HL2 yields [(Me2Sn)2(L2)3(OSO2Me)], 5 as partially disproportionated product of Me2Sn(L2)OSO2Me. The solid-state structures of 2-5 reveal variable modes of coordination of the ligands to afford molecular and polymeric motifs.

Occupational exposure to organotin substances: Development of a liquid chromatographic separation method for 11 organotin compounds in workplace air samples via HPLC-ICP-MS.

Organotin compounds (OTCs) are widely regulated but rank among the most used organometallic compounds in various industrial sectors. They are significantly more toxic than inorganic tin compounds. At workplaces, OTCs can be released as vapors or dust particles and can be absorbed by inhalation or skin contact. Occupational exposure thus represents a great risk for the absorption of OTCs for employees. Methods for OTCs speciation in workplace air monitoring currently do not exist. This study describes the development of a separation method for eleven in Germany regulated OTCs via HPLC-ICP-MS. The method allows a near baseline separation of MMT, MBT, MOT, MPhT, DMT, DBT, DPhT, TMT, TBT, TPhT and TTMT within 22 min on a C18 column and a ternary solvent and flow rate gradient using methanol, acetonitrile, and ultrapure water + 6% (v/v) acetic acid + 0.17% (m/v) α-tropolone. Ten analytes show linearity in the working range of 10 - 100 µg OTCs/L with R² > 0.999. Due to its high volatility the analyte TTMT showed a quadratic relationship between concentration and signal intensity with R² = 0.9998. The determination of the instrumental limits resulted in detection limits between 0.14 and 0.57 µg Sn/L and limits of quantification between 0.49 and 1.97 µg Sn/L. Over the course of this study thermal instability and cross reactivity of OTC in solution became apparent. Formation of two reaction products in mixed OTCs solutions have been observed. These effects will further be examined within development of appropriate sampling and sample preparation for workplace air to provide a suitable method for the determination of OTCs at workplaces according to normative references.

Assessment of toxicity, genotoxicity and oxidative stress in Fejervarya limnocharis exposed to tributyltin.

Tributyltin (TBT) is widely used in various commercial applications due to its biocidal properties. Toxicological and genotoxicological data on TBT exposure to amphibians is insufficient. Our study aimed to determine the acute toxicity and genotoxic potential of TBT in Fejervarya limnocharis tadpoles. Furthermore, oxidative stress was also investigated in TBT-treated tadpoles. Tadpoles of Gosner stage (26-30) were screened and subjected to increasing concentrations of TBT (0, 3, 7, 11, 15, 19, 23 µg/L) for determining the LC50 values for 24 h, 48 h, 72 h, and 96 h. LC50 values of TBT for 24 h, 48 h, 72 h, and 96 h were found to be 19.45, 15.07, 13.12, and 11.84 µg/L respectively. Based on the 96 h LC50 value (11.84 µg/L), tadpoles were exposed to different sub-lethal concentrations of TBT for the evaluation of its genotoxic potential and effects on oxidative balance. The role of TBT on survivability, growth, and time to metamorphosis was also assessed. TBT exposure significantly altered the life history traits measured, increased mortality, and delayed the time taken to metamorphosis. Results indicated significant induction of micronucleus (MN, p < 0.001) and other erythrocytic nuclear aberrations (ENA, p < 0.01) in the TBT-treated groups. Significant alterations in comet parameters and oxidative balance were also observed in the treated groups. The present study findings might add to the cause of the gradual population decline seen in the amphibians. This study also demonstrates the alteration of the life-history traits, oxidative balance, and DNA damage upon TBT exposure which can have long-term consequences for the anuran amphibian F. limnocharis.

Cellular and DNA Toxicity Study of Triphenyltin Ethyl Phenyl Dithiocarbamate and Triphenyltin Butyl Phenyl Dithiocarbamate on K562, Leukemia Cell Line.

INTRODUCTION: Continuous research for new effective drugs to treat cancer has improved our understanding on the mechanism of action of these drugs and paved new potential for their application in cancer treatments. In this study, organotin compounds known as triphenyltin ethyl phenyl dithiocarbamate and triphenyltin butyl phenyl dithiocarbamate were investigated for their toxicity on leukemia cell line (K562) and non-cancerous cell line (Chang liver cell and lung fibroblast, V79 cell). METHODS: MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes. RESULTS: The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 µM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 µM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects. CONCLUSION: Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.

Synthesis, characterization and discovery of multiple anticancer mechanisms of dibutyltin complexes based on salen-like ligands.

A series of novel dibutyltin complexes based on salen-like ligands (S01-S03) were synthesized and characterized using ultraviolet-visible spectra，infrared spectra, 1H, 13C, and 119Sn nuclear magnetic resonance, high-resolution mass spectrometry, X-ray crystallography, and thermogravimetric analysis. Complex S03 had excellent anticancer activity in vitro (IC50 = 1.5 ± 0.2 µM in CAL-27 cell lines), which highly activated ROS expression levels and induced apoptosis and cell cycle arrest at the G2/M phase. Interestingly, complex S03 induced cancer cell death through multiple mechanisms (mitochondrial pathway, ER-stress pathway, and DNA damage pathway). This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs in the future, and compounds with multiple anticancer mechanisms may be a new strategy for delaying or overcoming drug resistance to chemotherapy and target therapy.

Determination of organotin compounds in marine sediments from Arctic Svalbard and West Antarctic Fildes Peninsula.

This study investigated the contamination levels of five typical organotin compounds in Arctic and Antarctic marine sediments. Organotin total concentrations ranged from not detected (ND) to 37.9 ng Sn/g dw and from ND to 34.0 ng Sn/g dw in surface sediments of Svalbard and Fildes Peninsula, respectively. Dibutyltin accounted for 11.3 %-100 % of butyltins in Arctic sediments, whilst diphenyltin was the predominant phenyltin species in both Arctic and Antarctic. However, the concentrations of tributyltin and triphenyltin were lower than low-substituted organotins in the study areas, indicating the effectiveness of international ban on the use of triorganotin-based antifouling paints. No significant difference in organotin contamination was found between Arctic and Antarctic, although the time suffered from human interference was shorter in the Antarctic. Overall, these data can provide a diagnosis of recent organotin inputs in polar regions and serve as a baseline for future study assessing their local applications.

Occurrence of organotin compounds in food: increasing challenge of phenyltin compounds.

Concentrations and distribution for 16 organotin compounds were studied in all kinds of foods, including seafood, agricultural products, and wine. Meanwhile, the degradation of the TBT or TPhT was also evaluated. Concentrations of total organotins in seafood, agricultural products, and wine were 1047.2, 469.4, and 13.5 µg Sn/kg. Meanwhile, the most frequently detected organotin in three kinds of samples were TPhT, MPhT, and MPhT, respectively. The results demonstrated that phenyltin may probably become an emerging organotin pollutant. Regarding seafood, organotin concentrations of fish and mollusks were much higher than those of crustaceans. At the same time, a significant positive correlation was observed between the concentrations of TBT and MBT (p < 0.05), and between DBT and MBT(p < 0.0001). Moreover, TPhT was significantly and positively associated with DPhT (p < 0.0001), suggesting that TPhT was the precursor of DPhT. Apart from the likely illegal use of OTs as biocides in antifouling paints for ships, anthropogenic activity like agricultural activity or industrial activity also caused organotin contamination. Further research and more effective measures should be formulated to protect the food safety. Meanwhile, monitoring of the organotin contamination should not only in Qinhuangdao, but also expand to the cities along Bohai Bay.