Recognition of human telomeric G-quadruplex DNA by 1,5-disubstituted diethyl-amido anthraquinone derivative in different ion environments causing thermal stabilization and apoptosis.

Ligand binding to G-quadruplex (G4) structures at human telomeric DNA ends promotes thermal stabilization, disrupting the interaction of the telomerase enzyme, which is found active in 80-85% of cancers and serves as a molecular marker. Anthraquinone compounds are well-known G-quadruplex (G4) binders that inhibit telomerase and induce apoptosis in cancer cells. Our current investigation is based on 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione, a derivative of anthraquinone and its binding characterization with two different human telomeric DNA structures, wHTel26 and HTel22, in the effect of K+ and Na+ by using an array of biophysical, calorimetry, molecular docking and cell viability assay techniques. Binding constants (Kb) in the range of ∼105-107 M-1 and stoichiometries of 1:1, 2:1 & 4:1 were obtained from the absorbance, fluorescence, and circular dichroism study. Remarkable hypochromism (55, 97%) and ∼17 nm shift in absorbance, fluorescence quenching (95, 97%), the unaltered value of fluorescence lifetime, restoration of Circular Dichroism bands, absence of ICD band, indicated the external groove binding/binding somewhere at loops. This is also evident in molecular docking results, the ligand binds to groove forming base (G4, G5, G24, T25) and in the vicinity to TTA loop (G14, G15, T17) bases of wHTel26 and HTel22, respectively. Thermal stabilization induced by ligand was found greater in Na+ ion (27.5 °C) than (19.1 °C) in K+ ion. Ligand caused cell toxicity in MCF-7 cancer cell lines with an IC50 value of ∼8.4 µM. The above findings suggest the ligand, 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione could be a potent anticancer drug candidate and has great therapeutic implications.Binding of disubstituted amido anthraquinone derivative, 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione to human telomere HTel22 antiparallel conformation induced thermal stabilization.Communicated by Ramaswamy H. Sarma.

Cellular uptake of metal oxide-based nanocomposites and targeting of chikungunya virus replication protein nsP3.

Emergence of new pathogenic viruses along with adaptive potential of RNA viruses has become a major public health concern. Therefore, it is increasingly crucial to investigate and assess the antiviral potential of nanocomposites, which is constantly advancing area of medical biology. In this study, two types of nanocomposites: Ag/NiO and Ag2O/NiO/ZnO with varying molar ratios of silver and silver oxide, respectively have been synthesised and characterised. Three metal/metal oxide (Ag/NiO) composites having different amounts of Ag nanoparticles (NPs) anchored on NiO octahedrons are AN-5 % (5 % Ag), AN-10 % (10 % Ag) and AN-15 % (15 % Ag)) and three ternary metal oxide nanocomposites (Ag2O/NiO/ZnO) i.e., A/N/Z-1, A/N/Z-2, and A/N/Z-3 with different molar ratios of silver oxide (10 %, 20 % and 30 %, respectively) were evaluated for their antiviral potential. Cellular uptake of nanocomposites was confirmed by ICP-MS. Intriguingly, molecular docking of metal oxides in the active site of nsP3 validated the binding of nanocomposites to chikungunya virus replication protein nsP3. In vitro antiviral potential of nanocomposites was tested by performing plaque reduction assay, cytopathic effect (CPE) analysis and qRT-PCR. The nanocomposites showed significant reduction in virus titre. Half-maximal inhibitory concentration (IC50) for A/N/Z-3 and AN-5 % were determined to be 2.828 and 3.277 µg/mL, respectively. CPE observation and qRT-PCR results were consistent with the data obtained from plaque reduction assay for A/N/Z-3 and AN-5 %. These results have opened new avenues for development of nanocomposites based antiviral therapies.

Erratum: Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity.

[This corrects the article DOI: 10.1016/j.omtn.2022.11.008.].

Ag nanoparticles anchored on NiO octahedrons (Ag/NiO composite): An efficient catalyst for reduction of nitro substituted phenols and colouring dyes.

The development of an efficient sustainable catalyst for effective removal of hazardous chemicals, viz. nitrophenols and organic dyes, from wastewater is a challenging task. Herein, facile synthesis of Ag/NiO composites by anchoring Ag nanoparticles (NPs) on NiO octahedrons with different amounts of Ag NPs (AN-5% (5% Ag), AN-10% (10% Ag) and AN-15% (15% Ag)) has been demonstrated. SEM (scanning electron microscopic) and TEM (transmission electron spectroscopic) images ensured the proper anchoring of spherical Ag NPs (particle size = 16.54 ± 1.88 nm) on octahedron particles of NiO, which was also ensured by XPS (X-ray photoelectron spectroscopy) analysis. Moreover, the resulting composites have an average surface area (49-52 m2g‒1) and pore size (2.39-2.26 nm). All three synthesized Ag/NiO composites (100 µL) catalyzed the complete reduction of para-np (4-nitrophenol: 0.1587 mM) within 2-3 min in the presence of 0.04 M NaBH4. Among them, AN-5% has been chosen because of the lowest anchored Ag (5%) to obtain the optimized catalyst's amount (50 µL) and concentration of para-np (0.1587 mM). AN-5% also exhibited excellent catalytic activity towards different nitro substituted phenols, viz. ortho-np (2-nitrophenol), meta-np (3-nitrophenol), para-np (4-nitrophenol) and tri-np (2,4,6-trinitrophenol). AN-5% displayed ∼100% catalytic efficiency for reducing meta-np in 2 min with the apparent first order rate constant (kapp) and normalized rate constant (Knor) as 1.99 s-1 and 398.14 s-1 g-1, respectively. Additionally, AN-5% (29.41 µg mL-1) reduced >95% of the colouring dyes (10 ppm) such as CONG-R (congo red: 95% in 6 min), METH-O (methyl orange: 97.5% in 7 min), METH-B (methylene blue: 98.3% in 10 min) and RHOD-B (rhodamine B: 99.2% in 5 min). AN-5% not only demonstrated catalytic reduction towards individual pollutants, but also showed excellent activity for reduction of the mixtures of nitrophenols/dyes and for treatment of simulated industrial effluent samples (EFF1, EFF2) and a real industrial sample (textile dye-bath effluent). AN-5% can also be reused up to several cycles with almost same efficiency and followed the Langmuir-Hinshelwood apparent first order kinetics model.

Molecular rec§ognition of telomere DNA sequence by 2, 6 anthraquinone derivatives leads to thermal stabilization and induces apoptosis in cancer cells.

According to current research, anti-cancer anthraquinones impact telomere disruption and may interact with G-quadruplex DNA that triggers signaling to apoptosis. The present study represents the biophysical investigation of oxidative stress, late apoptosis, and induced senescence among cancer cells after binding laboratory synthesized piperidine-based anthraquinone derivatives, 2, 6- Bis [(3-piperidino)acetamido)]anthracene-9,10-dione (N1P) and 2, 6-Bis [piperidino)propionamido]anthracene-9,10-dione (N2P), with G-quadruplex DNA. We employed biophysical approaches to explore the interaction of synthetic anthraquinone derivatives with quadruplex DNA sequences to influence biological activities in the presence of K+ and Na+ cations. The binding affinity for N2P and N1P are Kb = 5.8 × 106 M-1 and Kb = 1.0 × 106 M-1, respectively, leading to hypo-/hyper-chromism with 5-7 nm red shift and significant fluorescence quenching and changes in ellipticity resulting in external binding of both the ligands to G-quadruplex DNA. Ligand binding induced enhancement of thermostability of G4 DNA is greater in Na+ environment (ΔTm = 34 °C) as compared to that in K+ environment (ΔTm = 21 °C), thereby restricting telomerase binding access to telomeres. Microscopic images of treated cells indicated cellular shape, nuclear condensation, and fragmentation alterations. The findings pave the path for therapeutic research, given the great potential of modifying anthraquinone substituent groups towards improved efficacy, ROS generation, and G-quadruplex DNA selectivity.

Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity.

G-quadruplex is a non-canonical secondary structure identified in the telomeric region and the promoter of many oncogenes. Anthraquinone derivatives, a well-known inducer of telomere disruption in malignant cells and activate the apoptotic pathway. We used biophysical and biochemical studies to confirm the interaction of synthesized anthraquinone derivatives with the human telomeric G-quadruplex sequence. The binding affinity of N-2DEA and N-1DEA are K b = 4.8 × 106 M-1 and K b = 7.6 × 105 M-1, respectively, leading to hypochroism, fluorescence quenching with minor redshift and ellipticity variations indicating ligand binding in the external groove. We found that sodium ions induced stabilization more rather than potassium ions. Molecular docking of complex demonstrates a molecule's exterior binding to a quadruplex. The investigation of ROS activity indicated that the cell initiates mortality in response to the IC50 concentration. Cellular morphology, nuclear condensation, and fragmentation were altered in the treated cell, impairing cellular function. Finally, the transcriptional regulatory study paves the way for drug design as an anti-cancer agent because of the tremendous possibilities of changing substituent groups on anthraquinones to improve efficacy and selectivity for G-quartet DNA. Our research focused on how ligand binding to telomere sequences induces oxidative stress and inhibits the growth of malignant cells.

Facile synthesis of ZnO-SnO2 anchored ZIF-8 nanocomposite: a potential photocatalyst.

For the first time, ZnO-SnO2 nanocomposite has been anchored (ZS@Z) on ZIF-8 (zeolitic imidazolate framework) surface and encapsulated (ZS@Z1, ZS@Z2 and ZS@Z3) within ZIF-8 matrix during the in situ synthesis of ZIF-8. ZnO-SnO2 nanocomposites were synthesized in various molar ratio of Zn and Sn, i.e. 1:1, 2:8, 4:6, 6:4 and 8:2 (abbreviated as ZS-11, ZS-28, ZS-46, ZS-64 and ZS-82) using sol-gel and by grinding method (abbreviated as ZS-A, ZS-B, ZS-C, ZS-D and ZS-E). As-synthesized ZnO-SnO2 nanocomposites have been well characterized using various spectroscopic techniques. Further, ZS-E nanocomposite was succesfully anchored and encapsulated within ZIF-8 due to its good photocatalytic activity. Morphology of ZnO-SnO2 nanocomposites and their composites (ZS@Z, ZS@Z1, ZS@Z2 and ZS@Z3) was ensured by SEM (scanning electron microscopy) and TEM (transmission electron microscopy) images. The lowering of band gap of ZIF-8 from 5.2 to 3.25/3.79 eV confirmed the proper anchored ZnO-SnO2@ZIF-8. Moreover, XPS analysis was also performed for the analysis of elemental composition of composites. In order to validiate thier photocatalytic application, adsorption capacity and photodegradation efficiency have been examined using methylene blue (MB) as model pollutant. It has been found that 10 mg of ZnO-SnO2 nanocomposite (ZS-E) exhibits maximum photodegradation efficiency (58.68%) towards MB ([MB] = 1.6 mg L-1) at pH = 7.89 while ZS@Z, ZS@Z1, ZS@Z2 and ZS@Z3 composites (10 mg, 0.5 mg mL-1) can degrade off 100%, 93%, 97% and 92% MB, respectively. Hence, ZS@Z, ZS@Z1, ZS@Z2 and ZS@Z3 composites exhibit enhanced photodegradation efficiency as compared to ZIF-8 and ZnO-SnO2 nanocomposites and can be used for water remediation.

Multi-core-shell composite SnO2NPs@ZIF-8: potential antiviral agent and effective photocatalyst for waste-water treatment.

With increasing environment pollution and bacterial transmitted viral diseases globally, the development of new, effective, and low-cost materials/strategies is the current major challenge. To combat with this alarming problem, three new multi-functional and thermally stable SnO2NPs@ZIF-8 composites (NC1, NC2, and NC3) were synthesized by a facile and sustainable approach involving in situ encapsulation of SnO2NPs (150, 300, and 500 µL suspension in methanol) within zeolitic imidazole framework at room temperature. The morphology and crystallinity of ZIF-8 remained unchanged upon the proper encapsulation of SnO2NPs in its matrix. Herein, for the first time, the antiviral potential of ZIF-8 and SnO2NPs@ZIF-8 against chikungunya virus is reported by investigating their cytotoxicity against Vero cell line (employing MTT ((3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide)) assay). The maximum non-toxic doses were 0.04 mg mL-1 for ZIF-8 and SnO2NPs@ZIF-8 and 0.1 mg mL-1 for SnO2NPs. Further, NC1 exhibited (based on plaque assay) reduction in viral load/titers up to > 80% during post-treatment and > 50% during pre-treatment, greater than that of ZIF-8 and SnO2NPs due to synergistic effect. Further, NC1 (10 mg) exhibited enhanced photocatalytic efficiency (≥ 96%) for degradation of methylene blue (0.5 × 10-5 M) at pH ˃ 7.0. The probable mechanism for their antiviral activity and photocatalytic activity has been discussed. The multi-functional composites can effectively be used to reduce water pollution and as remedy for mosquito/bacterial transmitted viral diseases.

New diorganotin(IV) derivatives of dipeptides: synthesis and characteristic spectral studies.

Some new diorganotin(IV) derivatives of the formulae, R2SnL, where R=Me, n-Bu, Ph, and n-Oct, and L is the dianion of histidinylalanine (H2L-1) and histidinylleucine (H2L-2) have been synthesized by the reaction of R2SnCl2 and the preformed sodium salt of the respective dipeptides. The bonding and coordination behaviour in these derivatives are discussed on the basis of FT-IR, multinuclear 1H, 13C and 119Sn NMR and 119Sn Mössbauer spectroscopic studies. These investigations suggest that dipeptides in R2SnL act as dianionic tridentate coordinating through the COO(-), NH2 and N(-)peptide groups. The 119Sn Mössbauer studies, together with the NMR data, suggest a trigonal bipyramidal geometry around tin in R2SnL with the alkyl/aryl groups and Npeptide in the equatorial positions, while a carboxylic oxygen and the amino nitrogen atom occupy the axial positions.

Synthesis and spectral studies of organotin(IV) 4-amino-3-alkyl-1,2,4-triazole-5-thionates: in vitro antimicrobial activity.

Some di- and triorganotin(IV) triazolates of general formula, R(4-n)SnLn (where n=2; R=Me, n-Bu and Ph; n=1; R=Me, n-Pr, n-Bu and Ph and HL=4-amino-3-methyl-1,2,4-triazole-5-thiol (HL-1); and 4-amino-3-ethyl-1,2,4-triazole-5-thiol (HL-2)) were synthesized by the reaction of R(4-n)SnCln with sodium salt of HL-1 and HL-2. The bonding and coordination behavior in these derivatives have been discussed on the basis of IR and 119Sn Mössbauer spectroscopic studies in the solid state. Their coordination behavior in solution is discussed by multinuclear (1H, 13C and 119Sn) NMR spectral studies. The IR and 119Sn Mössbauer spectroscopic studies indicate that the ligands, HL-1 and HL-2 act as a monoanionic bidentate ligand, coordinating through Sexo- and Nring. The distorted skew trapezoidal-bipyramidal and distorted trigonal bipyramidal geometries have been proposed for R2SnL2 and R3SnL, respectively, in the solid state. In vitro antimicrobial screening of some of the newly synthesized derivatives and of some di- and triorganotin(IV) derivatives of 3-amino-1,2,4-triazole-5-thiol (HL-3) and 5-amino-3H-1,3,4-thiadiazole-2-thiol (HL-4) along with two standard drugs such as fluconazole and ciprofloxacin have been carried out against the bacteria, viz. Staphylococcus aureus and Escherichia coli, and against some fungi, viz. Aspergillus fumigatus, Candida albicans, Candida albicans (ATCC 10231), Candida krusei (GO3) and Candida glabrata (HO5) by the filter paper disc method. The studied organotin(IV) compounds show mild antifungal activity as compared to that of fluconazole, however, they show almost insignificant activity against the studied Gram-positive (Staphylococcus aureas) and Gram-negative (Escherichia coli) bacteria as compared to that of standard drug, ciprofloxacin.

Multifunctional CdSNPs@ZIF-8: Potential Antibacterial Agent against GFP-Expressing Escherichia coli and Staphylococcus aureus and Efficient Photocatalyst for Degradation of Methylene Blue.

Multifunctional novel core-shell composites, CdSNPs@ZIF-8, have been synthesized by in situ encapsulation of different amounts of CdSNPs (150, 300, and 500 µL suspension of CdSNPs in methanol) in ZIF-8 at room temperature. These composites have been characterized by powder X-ray diffraction, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy, high-resolution transmission electron microscopy (HRTEM), and diffuse reflectance spectroscopy techniques and Brunauer-Emmett-Teller surface analysis. XPS and HRTEM indicate the encapsulation of CdSNPs within ZIF-8 crystal without disturbing the crystal order of ZIF-8. The average size of embedded CdSNPs (determined by the particle size distribution from HRTEM) is found to be 16.34 nm. CdSNPs@ZIF-8 showed potential to be used as an antibacterial agent against the broad spectrum of bacterial strains such as Gram-positive Staphylococcus aureus and Gram-negative green fluorescent protein-expressing Escherichia coli in aqueous medium, as evident by various biophysical experiments, viz., 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, optical density and fluorescence spectroscopic studies, fluorescence and optical microscopic image analysis, disk diffusion assay, field emission scanning electron microscopy, and flow cytometry for reactive oxygen species induction assay. Further, the composite has been used as an efficient photocatalyst for the degradation of organic pollutants, such as methylene blue dye, in aqueous medium and found that the core-shell composite, CdSNPs@ZIF-8 (150 µL) (abbreviated as NC-1) (5 mg), exhibited higher photocatalytic activity (≈1.8 times) than CdSNPs for degradation of 90% of methylene blue (10 mL of 10 ppm) at pH ≥ 7 due to the synergetic effect. Therefore, in situ encapsulation of CdSNPs in ZIF-8 provides an easy executable measure for purification of wastewater effluents for the effective photocatalytic degradation of organic pollutants as well as to remove the bacterial contamination under sunlight.

Microwave-assisted synthesis of mixed ligands organotin(IV) complexes of 1,10-phenanthroline and l-proline: Physicochemical characterization, DFT calculations, chemotherapeutic potential validation by in vitro DNA binding and nuclease activity.

Diorganotin(IV) and triphenyltin(IV) derivatives of L-proline (HPro) having general formula R2Sn(Pro)2 (R=n-Bu (1), Ph (2)) and Ph3Sn(Pro) (3), respectively, and the mixed ligands di-/triorganotin(IV) derivatives of L-proline and 1,10-phenanthroline (phen) with general formula [R2Sn(Pro)(Phen)Cl] and [R3Sn(Pro)(Phen)] (where R=Me (4 and 7), n-Bu (5 and 8), Ph (6 and 9)), respectively, have been synthesized by microwave-assisted method and characterized by elemental analysis, IR, NMR (1H, 13C and 119Sn) and DART-mass spectral studies. The results suggest bicapped tetrahedron or a skew trapezoidal-bipyramid geometry for R2Sn(Pro)2, a distorted tetrahedral geometry for Ph3Sn(Pro) and a distorted octahedral geometry for [R2Sn(Pro)(Phen)Cl] and [Ph3Sn(Pro)(Phen)] around the Sn atom, and the same has been validated by density functional theory calculations (DFT). In vitro DNA binding studies of 1-9 have been investigated by UV-Vis, fluorescence and circular dichroism titrations, viscosity and DNA melting experiments. The observed hypochromic shift in UV-Vis and fluorescence studies evidenced a partial intercalative mode of binding of complexes to CT-DNA. The binding affinity and quenching ability have been quantified in terms of intrinsic binding constant (Kb) and Stern-Volmer quenching constant (Ksv). The determined values suggest that di- and triorganotin(IV) derivatives of L-proline possess lesser affinity to bind with CT-DNA in comparison to the mixed ligands di-/triorganotin(IV) derivatives of L-proline and 1,10-phenanthroline. The partial intercalative mode of binding of these complexes with CT DNA has also been supported by a change in the viscosity and melting point of DNA as well as a change in the intensity of positive and negative bands in circular dichroism spectra. The cleavage studies by agarose gel electrophoresis indicate effective cleavage of supercoiled plasmid DNA into its nicked form by all the complexes and even to its linear form in presence of 9.

Synthesis, spectral and thermal studies of some organotin(IV) derivatives of 5-amino-3H-1,3,4-thiadiazole-2-thione.

Some tri- and diorganotin(IV) compounds of the general formula, RnSnL4-n (where n=2, R=Me, n-Bu and Ph; n=3, R=Me, n-Bu, n-Pr and Ph; HL=5-amino-3H-1,3,4-thiadiazole-2-thione) have been synthesized by the reaction of RnSnCl4-n (where n=2 or 3, R=Me, n-Bu, n-Pr and Ph) and the sodium salt of the ligand. Oct2SnL2 was obtained by the reaction of Oct2SnO with HL in a 1:2 molar ratio under azeotropic removal of water. The bonding and coordination behavior in these derivatives are discussed on the basis of IR, Far-IR, multinuclear (1H, 13C and 119Sn) NMR and 119Sn Mössbauer spectroscopic studies. These investigations suggest that in all the compounds the ligand acts as monoanionic bidentate coordinating through ring N(3) and exocyclic S. Thermal studies of five compounds, viz., Ph3SnL, Me2SnL2, n-Bu2SnL2, Oct2SnL2 and Ph2SnL2 have been carried out in the temperature range 25-1000 degrees C using TG, DTG and DTA techniques under an atmosphere of dry nitrogen.

New triorganotin (IV) derivatives of dipeptides as models for metal-protein interactions: synthesis, structural characterization and biological studies.

New non-electrolytic triorganotin(IV) derivatives of dipeptides with general formulae R3Sn(HL), where R = Ph and HL = monoanion of glycylisoleucine (H2L-1), valylvaline (H2L-2), alanylvaline (H2L-3), leucylalanine (H2L-4), leucylleucine (H2L-5); R = n-Bu and HL = monoanion of glycylisoleucine (H2L-1) and leucylalanine (H2L-4); and R = Me and HL = monoanion of leucylalanine (H2L-4) have been synthesized and characterized on the basis of infrared, multinuclear 1H, 13C and 119Sn NMR and 119Sn Mössbauer spectroscopic studies. These investigations suggest that all the ligands in R3Sn(HL) act as monoanionic bidentates coordinating through the COO- and NH2 groups. The 119Sn Mössbauer studies, together with the NMR data, indicate that, for these polymeric derivatives, the polyhedron around tin in R3Sn(HL) is a trigonal-bipyramid with the three organic groups in the equatorial positions, while the axial positions are occupied by a carboxylic oxygen and the amino nitrogen atom from the adjacent molecule. The anti-inflammatory and cardiovascular activities and toxicity of all these compounds have been determined. Four of the complexes have also been screened against some of the chosen bacterial and fungal strains. The Ph3Sn(IV) compounds exhibit better anti-inflammatory and cardiovascular activities in comparison to the Me3Sn(IV) and n-Bu3Sn(IV) analogues. n-Bu3Sn(Gly-Ile) and Ph3Sn(Ala-Val) exhibit good antibacterial activity against all the chosen strains.

Conventional and microwave-assisted synthesis, characterization, DFT calculations, in vitro DNA binding and cleavage studies of potential chemotherapeutic diorganotin(IV) mandelates.

Diorganotin(IV) complexes of the general formulae {[R2Sn(L)]2O}(R=Me (1), n-Bu (2), and n-Oct (3); L=anion of mandelic acid) and {[R2Sn(L)]2Cl2}(R=Ph (4)) have been synthesized by conventional thermal method (1a-3a), except 4a and by microwave-assisted reactions (1b-4b). The elemental analysis, IR, NMR ((1)H, (13)C and (119)Sn) and ESI-MS/DART-mass spectral studies revealed that dimeric 1:1 complexes with SnOSn bridges (1-3) are formed possessing distorted trigonal bipyramidal geometry around the Sn atoms, except 4b which exhibits octahedral geometry with SnClSn bridges. The proposed geometries have been validated by density functional theory calculations. Thermal behavior of 1b-4b, studied by using thermogravimetry (TG), differential thermal analysis (DTA) and derivative thermogravimetric (DTG) techniques, indicated that all except 4b are stable up to 200°C. In vitro interaction studies of 1b-4b with CT-DNA were performed by UV-Vis, fluorescence titrations and results suggest that the complexes are binding to DNA via an intercalative mode. The binding affinity and quenching ability were quantified in terms of intrinsic binding constant (Kb) (3.74×10(4)M(-1), 2b; >3.67×10(4)M(-1), 4b; >3.03×10(4)M(-1), 3b; >0.72×10(4)M(-1), 1b) and Stern-Volmer quenching constant (Ksv) (2.16×10(5), 2b; >1.73×10(5), 4b; >1.66×10(5)3b; >1.51×10(5), 1b) which showed high binding affinity of 2b with CT-DNA. The cleavage studies of 1b-4b with pBR322 plasmid DNA was ascertained by agarose gel electrophoresis. They exhibited effective cleavage of supercoiled plasmid DNA into its nicked form (1b, 3b, 4b) and even into its linear form in presence of 2b.

New triorganotin(IV) derivatives of dipeptides as anti-inflammatory-antimicrobial agents.

New triorganotin(IV) derivatives of dipeptides with general formulae R(3)Sn(HL), where R = Me and/or n-Bu and/or Ph and HL is the monoanion of glycylglycine (H(2)L-1), glycylvaline (H(2)L-2), glycylleucine (H(2)L-3), glycyltryptophane (H(2)L-4) and glycyltyrosine (H(2)L-5) have been synthesized and characterized on the basis of infrared, multinuclear NMR and (119)Sn Mossbauer spectroscopic studies. All the newly synthesized compounds were examined for their in vivo anti-inflammatory activity (using the carrageenan-induced paw edema bioassay in rats), acute toxicity (LD(50)) and cardiovascular activity. These compounds were also screened for their in vitro antimicrobial activity against Staphylococcus aureus Mau (29/58) and (78/71), Bacillus subtilis (18/64), Escherichia coli (326/71), Candida albicans (Pn-10), Microsporum gypseum and Euglena gracillis. The results revealed that triphenyltin(IV) derivatives exhibited anti-inflammatory activity comparable to that of phenylbutazone with high safety margin (LD(50) > 500 mg kg(-1)). Further Ph(3)Sn(Gly-Val) displays a potent cardiovascular activity. Moreover, most of the compounds displayed appreciable antibacterial activities when compared with ampicillin and norfloxacin. Compounds Ph(3)Sn(Gly-Gly) and Ph(3)Sn(Gly-Val) are the most distinctive derivatives identified in the present study because of their promising in vivo anti-inflammatory activity and in vitro antibacterial activity against gram-positive and -negative bacteria.

New organotin(IV) ascorbates: synthesis, spectral characterization, biological and potentiometric studies.

New organotin(IV) ascorbates of the general formulae R(3)Sn(HAsc) (where R = Me , n-Pr, n-Bu and Ph) and R(2)Sn(Asc) (where R = n-Bu and Ph) have been synthesized by the reaction of R(n)SnCl(4-n) (where n = 2 or 3) with monosodium-l-ascorbate. The bonding and coordination behaviour in these complexes are discussed on the basis of UV-Vis, IR, Far-IR, (1)H and (13)C NMR, and (119)Sn Mossbauer spectroscopic studies. L-Ascorbic acid acts as a monoanionic bidentate ligand in R(3)Sn(HAsc) coordinating through O(1) and O(3). The Mossbauer studies together with IR and NMR studies suggest that for these polymeric derivatives, the polyhedron is trigonal bipyramidal around tin with three organic groups in the equatorial positions. In R(2)Sn(Asc), L-ascorbic acid acts as dianionic tetradentate ligand and a polymeric structure with octahedral geometry around tin with trans organic groups has been tentatively proposed. The complexes have been assayed for their anti-inflammatory and cardiovascular activity. Ph(2)Sn(Asc) has been found to show the highest activity among the studied complexes. It is suggested on the basis of potentiometric studies of Me(2)Sn(IV) and Me(3)Sn(IV) systems with L-ascorbic acid that under physiological conditions (pH = 7.0) Me(2)Sn(HAsc)(OH) (approximately 60%), Me(2)Sn(OH)(2) (approximately 40%) and Me(3)Sn(HAsc) (approximately 60%), Me(3)Sn(OH) (approximately 40%), respectively, are existing, which may be responsible for their biological activities.

Synthesis, spectral characterization and biological studies of some organotin(IV) complexes of L-proline, trans-hydroxy-L-proline and L-glutamine.

New organotin(IV) complexes of the general formula R3Sn(L) (where R=Me, n-Bu and HL=L-proline; R=Me, Ph and HL=trans-hydroxy-L-proline and L-glutamine) and R2Sn(L)2 (where R=n-Bu, Ph and HL=L-proline; R=Ph, HL=trans-hydroxy-L-proline) have been synthesized by the reaction of RnSnCl(4-n) (where n=2 or 3) with sodium salt of the amino acid (HL). n-Bu2Sn(Pro)2 was synthesized by the reaction of n-Bu2SnO with L-proline under azeotropic removal of water. The bonding and coordination behavior in these complexes have been discussed on the basis of IR and 119Sn Mössbauer spectroscopic studies in the solid-state. Their coordination behavior in solution has been discussed with the help of multinuclear (1H, 13C and 119Sn) NMR spectral studies. The 119Sn Mössbauer and IR studies indicate that L-proline and trans-hydroxy-L-proline show similar coordination behavior towards organotin(IV) compounds. Pentacoordinate trigonal-bipyramidal and hexacoordinate octahedral structures, respectively, have been proposed for the tri- and diorganotin(IV) complexes of L-proline and trans-hydroxy-L-proline, in which the carboxylate group acts as bidentate group. L-glutamine shows different coordination behavior towards organotin(IV) compounds, it acts as monoanionic bidentate ligand coordinating through carboxylate and amino group. The triorganotin(IV) complexes of L-glutamine have been proposed to have trigonal-bipyramidal environment around tin. The newly synthesized complexes have been tested for their antiinflammatory and cardiovascular activities. Their LD50 values are >1000 mg kg-1.

New diorganotin(IV) derivatives of 7-hydroxycoumarin (umbelliferone) and their adducts with 1,10-phenanthroline.

New diorganotin(IV) derivatives of the general formula R2Sn(Umb)2 (where R = n-Bu, n-Oct and Ph; Umb = umbelliferone anion) have been synthesized either by the reaction of R2SnO with umbelliferone under azeotropic removal of water or by the reaction of R2SnCl2 with sodium salt of umbelliferone. Further, the adducts of the general formula R2Sn(Umb)2.phen (where R = n-Bu and n-Oct; phen = 1,10-phenanthroline) have also been synthesized by the interaction of R2Sn(Umb)2 with 1,10-phenanthroline. The bonding and coordination behavior in these derivatives are discussed on the basis of IR and 119Sn Mössbauer spectroscopic studies in solid state. Their coordination behavior in solution is discussed by the multinuclear (1H, 13C and 119Sn) NMR spectral studies. The Mössbauer and IR studies indicate that umbelliferone acts as a monoanionic bidentate ligand in R2Sn(Umb)2 coordinating through O(7) and O(1). A distorted octahedral geometry around tin has been proposed for R2Sn(Umb)2 as well as for R2Sn(Umb)2.phen in solid state. The newly synthesized derivatives have been tested for their anti-inflammatory and cardiovascular activities. The average LD50 value >1000 mg kg(-1) of these compounds indicates their safety margin.

Mode of action of tin-based anti-proliferative agents: Biological studies of organotin(IV) derivatives of fatty acids.

Some organotin(IV) carboxylates of the general formula RnSn(L)m [n=3, m=1, R=Me, Pr, Bu and Ph; n=2, m=2, R=Me, Bu and Oct; L=anion of lauric (HLA), stearic (HSA) and myristic acid (HMA)] have been synthesized and characterized by various spectroscopic studies. Tri- and diorganotin(IV) carboxylates adopt trigonal-bipyramidal and octahedral geometry around tin atom, respectively. They have been screened in vitro for anti-tumor activity against cancer cell lines of human origin, viz. MCF-7 (mammary), HEK-293 (kidney), PC-3 (prostate), HCT-15 (colon) and HepG-2 (liver). Enzyme assays viz. lipid peroxidase, glutathione peroxidase, glutathione reductase and total glutathione assay have been carried out to explore the cause of their cytotoxiciy. The results indicate that ROS (reactive oxygen species) generation may be responsible for their cytotoxicity but elevation in LDH (lactate dehydrogenase) suggests that necrosis cannot be excluded. Further, DNA (deoxyribonucleic acid) fragmentation, acridine orange and comet assay support the fact that the apoptosis is the main cause of cytotoxicity of organotin(IV) carboxylates, whereas the necrosis plays a minor role. The anti-inflammatory activity evaluation shows that the complexes possess moderate activity. Results of acute toxicity of the complexes have also been discussed.