Organotin Research Articles

Engineered organotin(IV) and vanadium(V) derivatives with distinct coordination modes and luminescent properties for the efficient detection and quantification of permanganate ions.

The distinction in coordination modes of metal complexes leads to their versatile structural features and unique properties. Here, we report two tetradentate Schiff base ligands (H2L1 and H2L2) bearing N2O2 donor sets, tactically selected to provide distinct coordination modes with different metal ions. The ligands were utilized to synthesize their organotin(IV) (1-4) and vanadium(V) (5) derivatives. The synthesized compounds were characterized using elemental analysis, FT-IR spectroscopy, multi-nuclei NMR (1H, 13C, and 119Sn) spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. The organotin(IV) derivatives (1-4) displayed hepta-coordination around both the Sn centres as they were achieved in their dimeric form. Contrariwise, the vanadium(V) compound (5) was isolated as a mononuclear entity exhibiting penta-coordinated geometry around the vanadium centre. The variation in the coordination modes was evident in their UV-vis and fluorescence spectra. The organotin(IV) compounds (1-4) exhibited a strong emission band centred at 468nm when excited at a wavelength of 360nm whereas the vanadium(V) (5) derivative displayed poor fluorogenic response. Compound 1 was further explored for the fluorogenic chemo-sensing of permanganate ions (MnO4-) amongst various anions by quenching response. A detailed investigation of the recognition of permanganate ions was accomplished by spectrofluorometric, spectroscopic (119Sn NMR), mass spectrometric, and computational studies.

Diorganotin(IV) N-methyl-N-phenethyldithiocarbamate Compounds Induce Cytotoxicity via Apoptosis in K562 Human Erythroleukaemia Cells

Imatinib mesylate (IM), a leading treatment for chronic myeloid leukaemia (CML), has sparked worries about the possibility of CML patients developing a resistance to it. As a result, researchers are becoming more interested in organotin(IV) compounds due to their strong potential to be developed as anticancer agents and employed as an option to address the issues regarding IM-resistance therapy. Generally, this study is to determine the cytotoxicity induced by diorganotin(IV) dithiocarbamate compounds in K562 human erythroleukaemia cells. The two novel diorganotin(IV) compounds namely diphenyltin(IV) N-methyl-N-phenethyldithiocarbamate (C1) and dibutyltin(IV) N-methyl-N-phenethyldithiocarbamate (C2) were assessed their cytotoxicity via MTT [3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and mode of cell death via Annexin V-FITC/PI assay with the duration treatment of 24 h. Both compounds displayed strong cytotoxicity in K562 cells. At concentration of 4.2 µM for C1 and 1.6 µM for C2, both compounds were able to induce 49.70% and 46.83% apoptotic events, respectively. The changes in cells' morphological can also be seen 24 h after being exposed to the compounds at their respective IC50 doses. The findings demonstrated that the morphology of the cells was similar to apoptotic features, including cell shrinkage and the production of apoptotic bodies, meanwhile, the low levels of necrotic cells (<1%) also can be seen via cell lysis. In conclusion, both compounds possess the potential as antileukaemia drugs nevertheless, further studies on their action mechanism are required to ratify their qualities and suitability in the research of anticancer drugs development.

Tin-Free Synthesis of 2,2′-Biphenyl Gold(III) Complexes Using Dibenzosilol

Gold(III) complexes with dianionic 2,2′-biphenyl ligands stand out for their oxophilic Lewis acid character in combination with a stable and well-defined square planar geometry. They have been demonstrated to be unique and efficient chiral (pre)catalysts. Furthermore, their chemical and physical properties make them interesting for stoichiometric studies as well as organic electronics. These complexes are commonly prepared by transmetallating the bph ligand from undesirable and potentially toxic organotin compounds onto gold salts, making their synthesis problematic for health and the environment. Here, we present a tin-free synthesis using stable and nontoxic dibenzosilol as a transmetallating agent, accessing the same range of gold complexes as the dibenzostannanol-based synthesis. Furthermore, we confirm that corresponding isonitrile gold(III) complexes can be transformed into carbene gold(III) complexes by the nucleophilic attack of amines, opening up the route to new gold(III) catalyst design strategies.

A Theoretical Study of Organotin Binding in Aromatase.

The widely used organotin compounds are notorious for their acute toxicity. Experiments revealed that organotin might cause reproductive toxicity by reversibly inhibiting animal aromatase functioning. However, the inhibition mechanism is obscure, especially at the molecular level. Compared to experimental methods, theoretical approaches via computational simulations can help to gain a microscopic view of the mechanism. Here, in an initial attempt to uncover the mechanism, we combined molecular docking and classical molecular dynamics to investigate the binding between organotins and aromatase. The energetics analysis indicated that the van der Waals interaction is the primary driving force of binding the organic tail of organotin and the aromatase center. The hydrogen bond linkage trajectory analysis revealed that water plays a significant role in linking the ligand-water-protein triangle network. As an initial step in studying the mechanism of organotin inhibiting aromatase, this work provides an in-depth understanding of the binding mechanism of organotin. Further, our study will help to develop effective and environmentally friendly methods to treat animals that have already been contaminated by organotin, as well as sustainable solutions for organotin degradation.

Postnatal exposure to trimethyltin chloride induces retinal developmental neurotoxicity in mice via glutamate and its transporter related changes

Exposure to toxic substances during postnatal period is one of the major factors causing retinal developmental defects. The developmental toxicity of trimethyltin chloride (TMT), a byproduct of an organotin compound widely used in agriculture and industrial fields, has been reported; however, the effect on the mammalian retina during postnatal development and the mechanism have not been elucidated to date. We exposed 0.75 and 1.5 mg/kg of TMT to neonatal ICR mice (1:1 ratio of male and female) up to postnatal day 14 and performed analysis of the retina: histopathology, apoptosis, electrophysiological function, glutamate concentration, gene expression, and fluorescence immunostaining. Exposure to TMT caused delayed eye opening, eye growth defect and thinning of retinal layer. In addition, apoptosis occurred in the retina along with b-wave and spiking activity changes in the micro-electroretinogram. These changes were accompanied by an increase in the concentration of glutamate, upregulation of astrocyte-related genes, and increased expression of glial excitatory amino acid transporter (EAAT) 1 and 2. Conversely, EAAT 3, 4, and 5, mainly located in the neurons, were decreased. Our results are the first to prove postnatal retinal developmental neurotoxicity of TMT at the mammalian model and analyze the molecular, functional as well as morphological aspects to elucidate possible mechanisms: glutamate toxicity with EAAT expression changes. These mechanisms may suggest not only a strategy to treat but also a clue to prevent postnatal retina developmental toxicity of toxic substances.

Synthesis and Applications of Organotin(IV) Compounds: Mini Review

Organotin(IV) compounds have seen a marked increase in industry utilization over the years and exhibited enormous economic benefits as well as environmental costs due to their numerous industrial, medical, and agricultural uses and other applications. The present review is a continuation of aseries of reviews on the use of organotin(IV), chemicals, synthesis, characteristics and geometry as well as the industrial and biological applications.

Development of a yeast reporter gene assay to detect ligands of freshwater cladoceran Daphnia magna ultraspiracle, a homolog of vertebrate retinoid X receptors.

Endocrine-disrupting chemicals (EDCs) often affect homeostatic regulation in living organisms by directly acting on nuclear receptors (NRs). Retinoid X receptors (RXRs), the most highly conserved members of the NR superfamily during evolution, function as partners to form heterodimers with other NRs, such as retinoic acid, thyroid hormone, and vitamin D3 receptors. RXRs also homodimerize and induce the expression of target genes upon binding with their natural ligand, 9-cis-retinoic acid (9cRA), and typical EDCs organotin compounds, such as tributyltin and triphenyltin. In the present study, we established a new yeast reporter gene assay (RGA) to detect the ligands of freshwater cladoceran Daphnia magna ultraspiracle (Dapma-USP), a homolog of vertebrate RXRs. D.magna has been used as a representative crustacean species for aquatic EDC assessments in the Organization for Economic Corporation and Development test guidelines. Dapma-USP was expressed along with the Drosophila melanogaster steroid receptor coactivator Taiman in yeast cells carrying the lacZ reporter plasmid. The RGA for detecting agonist activity of organotins and o-butylphenol was improved by use of mutant yeast strains lacking genes encoding cell wall mannoproteins and/or plasma membrane drug efflux pumps as hosts. We also showed that a number of other human RXR ligands, phenol and bisphenol A derivatives, and terpenoid compounds such as 9c-RA exhibited antagonist activity on Dapma-USP. Our newly established yeast-based RGA system is valuable as the first screening tool to detect ligand substances for Dapma-USP and for evaluating the evolutionary divergence of the ligand responses of RXR homologs between humans and D.magna.

Biological Evaluation of Triorganotin Derivatives as Potential Anticancer Agents.

Metal-derived platinum complexes are widely used to treat solid tumors. However, systemic toxicity and tumor resistance to these drugs encourage further research into similarly effective compounds. Among others, organotin compounds have been shown to inhibit cell growth and induce cell death and autophagy. Nevertheless, the impact of the ligand structure and mechanisms involved in the toxicity of organotin compounds have not been clarified. In the present study, the biological activities of commercially available bis(tributyltin) oxide and tributyltin chloride, in comparison to those of specially synthesized tributyltin trifluoroacetate (TBT-OCOCF3) and of cisplatin, were assessed using cells with different levels of tumorigenicity. The results show that tributyltins were more cytotoxic than cisplatin in all the tested cell lines. NMR revealed that this was not related to the interaction with DNA but to the inhibition of glucose uptake into the cells. Moreover, highly tumorigenic cells were less susceptible than nontumorigenic cells to the nonunique pattern of death induced by TBT-OCOCF3. Nevertheless, tumorigenic cells became sensitive when cotreated with wortmannin and TBT-OCOCF3, although no concomitant induction of autophagy by the compound was detected. Thus, TBT-OCOCF3 might be the prototype of a family of potential anticancer agents.

Series of Organotin(IV) Compounds with Different Dithiocarbamate Ligands Induced Cytotoxicity, Apoptosis and Cell Cycle Arrest on Jurkat E6.1, T Acute Lymphoblastic Leukemia Cells.

The discovery of cisplatin has influenced scientists to study the anticancer properties of other metal complexes. Organotin(IV) dithiocarbamate compounds are gaining attention as anticancer agents due to their potent cytotoxic properties on cancer cells. In this study, a series of organotin compounds were assessed for their toxic effects on the Jurkat E6.1 cell line. WST-1 assay was used to determine the cytotoxic effect of the compounds and showed that six out of seven organotin(IV) dithiocarbamate compounds exhibited potent cytotoxic effects toward T-lymphoblastic leukemia cells, Jurkat E6.1 with the concentration of IC50 ranging from 0.67-0.94 µM. The apoptosis assay by Annexin V-FITC/PI staining showed that all tested compounds induced cell death mainly via apoptosis. Cell cycle analysis assessed using RNase/PI staining showed that organotin(IV) dithiocarbamate compounds induced cell cycle arrest at different phases. In conclusion, the tested organotin(IV) dithiocarbamate compounds demonstrated potent cytotoxicity against Jurkat E6.1 cells via apoptosis and cell cycle arrest at low IC50 value. However, further studies on the mechanisms of action are required to probe the possible potential of these compounds on leukemia cells before they can be developed into anti-leukemic agents.

Comparative analysis of morphological and biochemical changes after a single intragastric administration of hybrid organotin compounds

Introduction. Organotin compounds are promising candidates for antitumor drugs. Identification of pathogenetic features of the general toxic effect of hybrid organotin compounds during the period of the greatest severity of the intoxication clinical picture will allow to estimate the risk of hepatotoxic and nephrotoxic complications with the administration of bis (3,5–di– tert–butyl–4–hydroxyphenylthiolate) dimethyltin (Me-3) and ((3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenyltin (M-e5) as chemotherapeutic agents.Аim: To conduct a comparative analysis of morphological and biochemical changes with a single intragastric administration of hybrid organotin compounds Me-3 and Me-5 in the maximum tolerated dose (MTD) on the 7th day of the toxic process development.Material and Methods. Hybrid organotin compounds Me-3 and Me-5 were administered once intragastrically to Wistar rats (females) at a MTD of 2000 mg/kg and 750 mg/kg, respectively. Biochemical and morphological studies were carried out on the 7th day of the development of intoxication symptoms according to standard methods.Results. With the introduction of Me-3 and Me-5 in the liver, signs of fatty dystrophy of varying severity were revealed, with a predominant lesion of centrolobular hepatocytes, an increase in the size of portal tracts due to edema and fibrosis, and scant lymphocytic infiltration. With the introduction of Me-5, morphological changes were more severe, with the involvement of the vascular bed of the organ in the process. When the tested compounds were administered in the kidneys, the same type of damage to the glomerular apparatus and renal tubules was recorded, characteristic of toxic nephropathy. Unidirectional changes in the blood of experimental animals were revealed in the group of nonspecific biochemical markers of cytolysis: a moderate decrease in transaminase activity and an increase in the activity of creatine kinase (CC), lactate dehydrogenase (LDH) and creatinine levels. The process of formation of urea and protein synthesis was functionally preserved.Conclusion. On the 7th day of the development of intoxication with a single intragastric administration of hybrid organotin compounds Me-3 and Me-5 in the maximum tolerated doses, biochemical and morphological changes in the body of animals could be attributed to a moderate degree of severity.

Joint effects of temperature and copper exposure on developmental and gene-expression responses of the marine copepod Tigriopus japonicus.

There is growing contamination of copper (Cu) in the marine environment, particularly after the ban of organotin compounds and the increase of the use of Cu-based antifouling paints. Although there are increasing research interests in temperature-dependent chemical toxicity to aquatic organisms, most existing studies focused on acute impacts of chemicals at high concentrations. This study aimed to investigate the interacting effect of temperature and copper exposure at environmentally relevant concentrations on survival and development in the marine copepod Tigriopus japonicus with a partial life-cycle toxicity test. Expressions of five stress response genes in the copepod, namely two glutathione S-transferases (GST-S and GST-O), two heat shock proteins (HSP70 and HSP90), and glutathione reductase (GR) were also investigated. The copepod's survival was significantly impaired at 15 °C after development to adult stage, while its developmental time reduced significantly with increasing temperature. Copper at the two environmentally relevant test concentrations had no significant impacts on these apical endpoints whereas the interaction between Cu and temperature was more significant in modulating gene expressions. GST-S, GST-O and HSP90 genes in copepods exposed to 100 µg Cu L-1 were significantly upregulated at 20 °C. At 32 °C, most genes were either insignificantly expressed or down-regulated, compared to the control, likely suggesting that thermal stress inhibited the copepod's antioxidative defense system. Overall, the results revealed that the joint Cu and thermal stresses have significantly elicited antioxidative system in the copepods. It clearly demonstrated the need for more fundamental studies about potential impacts of different environmental factors such as temperature on chemical toxicity under realistic scenario of marine pollution.

Combined effect of microplastic and triphenyltin: Insights from the gut-brain axis

Microplastics (MPs), an emerging group of pollutants, not only have direct toxic effects on aquatic organisms but also cause combined toxicity by absorbing other pollutants. Triphenyltin (TPT), one of the most widely used organotin compounds, has adverse effects on aquatic organisms. However, little is known about the combined toxicity of MPs and TPT to aquatic organisms. To investigate the individual and combined toxicity of MPs and TPT, we selected the common carp (Cyprinus carpio) for a 42-day exposure experiment. Based on the environmental concentrations in a heavily polluted area, the experimental concentrations of MPs and TPT were set at 0.5 mg L−1 and 1 μg L−1, respectively. The effects of MPs combined with TPT on the carp gut–brain axis were evaluated by detecting gut physiology and biochemical parameters, gut microbial 16S rRNA, and brain transcriptome sequencing. Our results suggest that a single TPT caused lipid metabolism disorder and a single MP induced immunosuppression in carp. When MPs were combined with TPT, the involvement of TPT amplified the immunotoxic effect induced by MPs. In this study, we also explored the gut–brain axis relationship of carp immunosuppression, providing new insights for assessing the combined toxicity of MPs and TPT. At the same time, our study provides a theoretical basis for evaluating the coexistence risk of MPs and TPT in the aquatic environment.

Characteristics, sources and health risks of organotin compounds in marine organisms from the seas adjacent to the eastern ports of China

Organotin compounds (OTCs), being widely used as antifouling coatings on ships, are defined as endocrine-disrupting chemicals by the EPA due to their harmful effects on marine organisms. The eastern coast of China has developed abundant maritime transportation and fishery industries but the associated OTC pollution can pose potential health risks. In the present study, 20 species of marine organisms (including mollusks, crustaceans and fish) were collected from the seas adjacent to the eastern ports of China and 6 OTCs (ie, tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT) and triphenyltin (TPhT), diphenyltin (DPhT) and monophenyltin (MPhT)) were analyzed using GC-MS/MS. ∑OTCs in marine organisms ranged from 0.81 to 2900 ng Sn g−1 dw with the mean of 130 ng Sn g−1 dw, being at a comparatively moderate level across the world. PhTs were the dominant pollutants with the contribution up to 51%–87%. Spatially, the highest concentration of OTCs occurred in marine organisms from the ports in the Southeast Coast, and mollusks were more likely to accumulate OTCs than other species. BT concentrations in seafood decreased significantly after the implementation and enforcement of the TBT ban. The source analysis showed that BTs detected in current biota are mainly from historical exposure to antifouling coating on ships. However, PhTs may be closely associated with coastal aquaculture as well as terrestrial agriculture-related activities. The commercially important fishes were recovered a higher level of ∑OTCs than others suggesting a potential risk for protein uptake. Health risks via seafood consumption caused by OTCs were not high but children are exposed to the highest risk, followed by adolescents and adults respectively. In the future, continuous monitoring of OTCs, especially PhTs, in marine organisms from the eastern ports of China is still necessary, and effective measures to protect marine ecosystems and human health need to be taken.

Progress of Metal-Based Anticancer Chemotherapeutic Agents in Last two Decades and their Comprehensive Biological (DNA/RNA Binding, Cleavage and Cytotoxicity Activity) Studies.

During last two decades, there has been an enormous growth in the discovery of innovative active inorganic anticancer complexes (exerting remarkable cytotoxicity at sub micro-molar levels) derived from myriad ligand scaffolds, mainly acting on cancerous vs healthy cells by either halting or inhibiting their uncontrolled growth. The phenomenal success of cisplatin to treat numerous forms of solid malignancies has placed metal-based drugs to the forefront of treatment strategies against cancers. More than 10,000 platinum anticancer complexes have been developed during the past 40 years, but only five drugs have been approved for usage in humans while ten more complexes are currently undergoing clinical trials. Most of the compounds have failed either at R&D stages or in preclinical trails. This has led to extensive investigations by researchers of medicinal chemistry, including our group to design and prepare tailored 3d-metallo-drugs and organotin(IV) compounds from some naturally occurring bioactive compounds, such as amino-acids, peptides, chromone derivatives and NSAID's etc. that were used either alone or in cocktail combination, capable of specifically targeting DNA, lnc RNAs and proteins. Furthermore, 3d-metal ions such as copper, cobalt and zinc etc. incorporated in these ligand framework are biocompatible and induce a unique multi-modal mechanism of cytotoxic action involving angiogenesis, ROS-induced DNA damage, apoptosis by p53 mitochondrial genes and caspases etc. The results observed a positive correlation between the binding affinity of complexes with DNA (as quantified by intrinsic binding constant values) and their cytotoxic behavior. Complexes with high DNA binding propensity were typically lethal against a diverse panel of malignant cell types compared to normal cells.

Comparative analysis of morphological and biochemical changes after a single intragastric administration of hybrid organotin compounds

Introduction. Organotin compounds are promising candidates for antitumor drugs. Identification of pathogenetic features of the general toxic effect of hybrid organotin compounds during the period of the greatest severity of the intoxication clinical picture will allow to estimate the risk of hepatotoxic and nephrotoxic complications with the administration of bis (3,5–di–tert–butyl–4–hydroxyphenylthiolate) dimethyltin (Me-3) and ((3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenyltin (M-e5) as chemotherapeutic agents.The aim of the study is to conduct a comparative analysis of morphological and biochemical changes with a single intragastric administration of hybrid organotin compounds Me–3 and Me-5 in the maximum tolerated dose (MTD) on the 7th day of the toxic process development.Material and Methods. Hybrid organotin compounds Me-3 and Me-5 were administered once intragastrically to Wistar rats (females) at a MTD of 2000 mg/kg and 750 mg/kg, respectively. Biochemical and morphological studies were carried out on the 7th day of the development of intoxication symptoms according to standard methods.Results. With the introduction of Me-3 and Me-5 in the liver, signs of fatty dystrophy of varying severity were revealed, with a predominant lesion of centrolobular hepatocytes, an increase in the size of portal tracts due to edema and fibrosis, and scant lymphocytic infiltration. With the introduction of Me-5, morphological changes were more severe, with the involvement of the vascular bed of the organ in the process. When the tested compounds were administered in the kidneys, the same type of damage to the glomerular apparatus and renal tubules was recorded, characteristic of toxic nephropathy. Unidirectional changes in the blood of experimental animals were revealed in the group of nonspecific biochemical markers of cytolysis: a moderate decrease in transaminase activity and an increase in the activity of creatine kinase (CC), lactate dehydrogenase (LDH) and creatinine levels. The process of formation of urea and protein synthesis was functionally preserved.Conclusion. On the 7th day of the development of intoxication with a single intragastric administration of hybrid organotin compounds Me-3 and Me-5 in the maximum tolerated doses, biochemical and morphological changes in the body of animals could be attributed to a moderate degree of severity.

Bioaccumulation of antifouling biocides in mangroves and seagrasses in coastal ecosystems

Abstract We measured the concentrations of antifouling biocides in sediment, mangrove leaves and seagrasses from Merambong and Tinggi Island, Johor, Malaysia to evaluate their contamination levels. Although the concentrations of tributyltin (TBT) in mangrove leaves in Merambong in 2013 were significantly lower than those in 2012, the Sea-Nine 211 concentration in 2013 was significantly higher than that in 2012, suggesting that the use of antifouling biocides changed from TBT to Sea-Nine 211. The concentration of each BT (butyltin) and PT (phenyltin) in the mangrove area was significantly higher than the corresponding concentration in the seagrass area in Merambong, but the concentrations of Sea-Nine 211, diuron, chlorothalonil, Irgarol 1051 and M1 in seagrasses were significantly higher than those in mangrove leaves. There were differences in the accumulation profiles of OTs (organotins) and alternative biocides between the seagrass shoots and roots. The concentration of OTs in the seagrass roots was almost the same or higher than those in the shoots, whereas those of alternative biocides shows the opposite pattern to the OTs. Significant high relationships were observed between stable carbon isotope (δ13C) and OTs, Sea-Nine 211 and Irgarols in mangrove leaves. The concentrations of these compounds increased along with the δ13C values of the mangroves. These results suggest that mangroves take up the bicarbonate ions and nutrients in sediment and/or seawater through their roots, along with OTs, Sea-Nine 211 and Irgarols which were accumulated in sediment.

Diorganotin(IV) complexes with hydroxamic acids derivatives of some histone deacetylases inhibitors

Organotin(IV) compounds show great potential as antitumor metallodrugs with lower toxicity and higher antiproliferative activity. Histone deacetylases (HDAC) inhibitors are characterised by high bioavailability and low toxicity. In this research, the two novel octahedral organotin(IV) complexes of physiologically active hydroxamate-based ligands, N-hydroxy-4-phenylbutanamide (HL1) and N-hydroxy-2-propylpentanamide (HL2), have been prepared and characterized using FTIR, 1H-, 13C- and 119Sn-NMR spectroscopy. Particular emphasis was put on the binding characteristics of ligands. The structures were additionally analysed by the density functional theory at B3LYP-D3BJ/6- -311++G(d,p)(H,C,N,O)/LanL2DZ(Sn) level. The theoretical IR and NMR spectra were compared to the spectroscopic data, and it was concluded that the predicted structures described well the experimental ones. The stability of different isomers of HL1 and HL2 was assessed by the natural bond orbital analysis, and the importance of intramolecular hydrogen bond was outlined. The interactions between donor atoms and Sn were investigated and correlated with the changes in chemical shift and the wavenumbers of characteristic vibrations.

Synthesis, Characterization and Cytotoxic Activity of Organotin(IV) Diisopropyldithiocarbamate Compounds Towards K562 Myeloid Leukaemia Cell Lines

In this work, two organotin(IV) compounds viz. triphenyltin(IV) diisopropyldithiocarbamate (1) and dimethyltin(IV) diisopropyldithio-carbamate (2) were synthesized via in situ method. Both synthesized organotin(IV) complexes were characterized by elemental, FT-IR and 1H, 12C and 119Sn NMR spectroscopies. The single-crystal structure of compound 1 was determined by X-ray single-crystal analysis. The elemental analysis data showed agreement with the suggested formulas of (C6H5)3Sn[S2CN(C3H7)2] (1) and (CH3)2Sn[S2CN(C3H7)2]2 (2). The important infrared absorbance peaks, ν(C=N) and ν(C=S), were detected in the ranges 1477-1474 cm-1 and 1038-997 cm-1 respectively. The chemical shift of carbon in the NCS2 group for compounds 1 and 2 was observed at 196.97 ppm and 198.11 ppm, respectively. The crystal structure of compound 1 showed that it is 5-coordinated and crystallized in a triclinic, P1 space group with the crystal cell parameter: a = 9.7572(1) Å, b = 11.7030(2) Å, c = 11.7602(2)Å, α = 74.419(1)°, β = 80.114(1)°, γ = 67.285(2)° and R = 0.002. The cytotoxicity (IC50) of these two compounds against K562 leukaemia cells was 0.25 μM and 4.3 μM, respectively, as assessed using MTT assay. In conclusion, the study demonstrates that both compounds showed potent cytotoxicity towards the K562 cell line tested, with compound 1 displaying a greater effect.

TESTING THE ACTIVITY OF THE SYNTHETIC COMPOUND DIPHENYLTIN (IV)N- BENZYL METHYL DITHIOCARBAMATE AGAINST BREAST CANCER MCF-7

Breast cancer is the leading cause of death, especially for women in Indonesia. Compounds that are widely used for anticancer at present are organotin compounds, one of which is dithiocarbamate compounds, with several reports of antifungal, antibacterial, anticancer, anti-alkylation, and apoptosis-inducing activities of metal dithiocarbamate complexes and their mixed ligands. The purpose of this study was to determine the activity test of the synthetic compound Diphenyltin (IV) N-Benzylmethyldithiocarbamate Against Breast Cancer MCF-7 using the MTT Assay (Microculture Tetrazolium Technique) Assay and to determine the functional group and structure of the compound Dibutyltin (IV) N-Benzylmethylditiocarbamate, used Spectrophotometer test FTIR (Fourier Transformed Infrared) and FTNMR (Nuclear Magnetic Resonance). From this study, it was found that the synthetic compound Diphenyltin (IV) N-Benzylmethyldithiocarbamate is a very potent compound in inhibiting the development and growth of MCF-7 breast cancer cells, because the compound has an IC50 value that is smaller than 10 g/ml which is 69, 640ppm.

Organotin Antifouling Compounds and Sex-Steroid Nuclear Receptor Perturbation: Some Structural Insights.

Organotin compounds (OTCs) are a commercially important group of organometallic compounds of tin used globally as polyvinyl chloride stabilizers and marine antifouling biocides. Worldwide use of OTCs has resulted in their ubiquitous presence in ecosystems across all the continents. OTCs have metabolic and endocrine disrupting effects in marine and terrestrial organisms. Thus, harmful OTCs (tributyltin) have been banned by the International Convention on the Control of Harmful Antifouling Systems since 2008. However, continued manufacturing by non-member countries poses a substantial risk for animal and human health. In this study, structural binding of common commercial OTCs, tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPT), diphenyltin (DPT), monophenyltin (MPT), and azocyclotin (ACT) against sex-steroid nuclear receptors, androgen receptor (AR), and estrogen receptors (ERα, ERβ) was performed using molecular docking and MD simulation. TBT, DBT, DPT, and MPT bound deep within the binding sites of AR, ERα, and Erβ, showing good dock score, binding energy and dissociation constants that were comparable to bound native ligands, testosterone and estradiol. The stability of docking complex was shown by MD simulation of organotin/receptor complex with RMSD, RMSF, Rg, and SASA plots showing stable interaction, low deviation, and compactness of the complex. A high commonality (50-100%) of interacting residues of ERα and ERβ for the docked ligands and bound native ligand (estradiol) indicated that the organotin compounds bound in the same binding site of the receptor as the native ligand. The results suggested that organotins may interfere with the natural steroid/receptor binding and perturb steroid signaling.