New triorganotin(iv) compounds with aromatic carboxylate ligands: synthesis and evaluation of the pro-apoptotic mechanism.

Three new organotin(iv) carboxylate compounds were synthesized and structurally characterized by elemental analysis and FT-IR and multinuclear NMR (1H, 13C, 119Sn) spectroscopy. Single X-ray crystallography reveals that compound C2 has a monoclinic crystal system with space group P21/c having distorted bipyramidal geometry defined by C3SnO2. The synthesized compounds were screened for drug-DNA interactions via UV-Vis spectroscopy and cyclic voltammetry showing good activity with high binding constants. Theoretical investigations also support the reactivity of the compounds as depicted from natural bond orbital (NBO) analysis using Gaussian 09. Synthesized compounds were initially evaluated on two cancer (HeLa and MCF-7) cell lines and cytotoxicity to normal cells was evaluated using a non-cancerous (BHK-21) cell line. All the compounds were found to be active, with IC50 values less than that of the standard drug i.e. cisplatin. The cytotoxic effect of the most potent compound C2 was confirmed by LDH cytotoxicity assay and fluorescence imaging after PI staining. Apoptotic features in compound C2 treated cancer cells were visualized after DAPI staining while regulation of apoptosis was observed by reactive oxygen species generation, binding of C2 with DNA, a change in mitochondrial membrane potential and expression of activated caspase-9 and caspase-3 in cancer cells. Results are indicative of activation of the intrinsic pathway of apoptosis in C2 treated cancer cells.

Synthesis of bio-mediated silver nanoparticles from Silybum marianum and their biological and clinical activities.

The purpose of current study was green synthesis of silver nanoparticles (AgNPs) from seeds and wild Silybum plants in comparison with their respective extracts followed by characterization and biological potency. The biologically synthesized AgNPs were subjected to characterization using techniques like XRD, FTIR, TEM, HPLC and SPE. Highly crystalline and stable NPs were obtained using Silybum wild plant (NP1) and seeds (NP3) with size range between 18.12 and 13.20 nm respectively. The synthesized NPs and their respective extracts revealed a vast range of biological applications showing antibacterial, antioxidant, anti-inflammatory, cytotoxic and anti-aging potencies. The highest antioxidant activity (478.23 ± 1.9 µM, 176.91 ± 1.3 µM, 83.5 ± 1.6% µgAAE/mg, 156.32 ± 0.6 µgAAE/mg) for ABTS, FRAP, FRSA, TRP respectively was shown by seed extract (NP4) followed by highest value of (117.35 ± 0.9 µgAAE/mg) for TAC by wild extract (NP2). The highest antifungal activity (13 mm ± 0.76) against Candida albicans was shown by NP3 while antibacterial activity of (6 mm against Klebsiella pneumonia) was shown by NP3 and NP4. The highest anti-inflammatory activity (38.56 ± 1.29 against COX1) was shown by NP2. Similarly, the high value of (48.89 ± 1.34 against Pentosidine-Like AGEs) was shown by NP4. Also, the high anti-diabetic activity (38.74 ± 1.09 against α-amylase) was shown by NP4. The extracts and the synthesized NPs have shown activity against hepato-cellular carcinoma (HepG2) human cells. The HPLC analysis revealed that the highest value of silymarin component (silybin B 2289 mg/g DW) was found for NP4. Silydianin is responsible for capping. Among the green synthesized AgNPs and the extracts used, the effect of NP4 was most promising for further use.

Synthesis, characterization, and anticancer activity of Schiff bases.

Five Schiff bases, 2-((3-chlorophenylimino)methyl)-5-(diethylamino)phenol (L1), 2-((2,4-dichlorophenylimino)methyl)-5-(diethylamino)phenol (L2), 5-(diethylamino)-2-((3,5-dimethylphenylimino)methyl)phenol (L3), 2-((2-chloro-4-methylphenylimino)methyl)-5-(diethylamino)phenol (L4), and 5-(diethylamino)-2-((2,6-diethylphenylimino)methyl)phenol (L5) were synthesized and characterized by elemental analysis, FT-IR, 1H and 13C NMR spectroscopy. Three of the compounds (L1, L2, and L4) were analyzed by single crystal X-ray diffraction: L1 and L2 crystallized in orthorhombic P212121 and Pca21 space group, respectively, while L4 crystallized in monoclinic P21/c space group. Theoretical investigations were performed for all the synthesized compounds to evaluate the structural details. Drug-DNA interaction studies results from UV-Vis spectroscopy and electrochemistry complement that the compounds bind to DNA through electrostatic interactions. The cytotoxicity of the synthesized compounds was studied against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21) by means of an MTT assay compared to carboplatin, featuring IC50 values in the micromolar range. The pro-apoptotic mechanism for the active compound L5 was evaluated by fluorescence microscopy, cell cycle analysis, caspase-9 and -3 activity, reactive oxygen species production, and DNA binding studies that further strengthen the results of that L5 is a potent drug against cancer.Communicated by Ramaswamy H. Sarma.

Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates.

This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

Potential bioactive Schiff base compounds: synthesis, characterization, X-ray structures, biological screenings and interaction with Salmon sperm DNA.

Three Schiff base compounds ofN'-substituted benzohydrazide and sulfonohydrazide derivatives: N'-(2-hydroxy-3-methoxybenzylidene)-4-tert-butyl- benzohydrazide (1), N'-(5-bromo-2-hydroxybenzylidene)-4-tert-butylbenzohydrazide (2) and N'-(2-hydroxy-3-methoxybenzylidene)-4-methylbenzenesulfonohydrazide (3) were synthesized and characterized by elemental analysis, FT-IR, (1)H, (13)C NMR spectroscopy and single crystal analysis. The title compounds have been screened for their biological activities including, antibacterial, antifungal, antioxidant, cytotoxic, enzymatic activities as well as interaction with SS-DNA which showed remarkable activities in each area of research. The DNA binding of the compounds 1-3 with SS-DNA has been carried out with absorption spectroscopy, which reveals the binding propensity towards SS-DNA via intercalation mode of interaction. The intercalative mode of interaction is also supported by viscometric results. The synthesized compounds were also found to be effective against alkaline phosphatase enzyme. They also show significant to good antimicrobial activity against six bacterial and five fungal strains. The MIC (minimum inhibitory concentration) for antibacterial activity ranges from 1.95-500 µg/mL. Compounds 1-3 show cytotoxic activity comparable to the control. At higher conc. (100 µg/L) compound 3 shows 100% activity means that it has killed all brine shrimps. They were also found to be effective antioxidant of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and show almost comparable antioxidant activity to that of the standard and known antioxidant, ascorbic acid.

Triphen-yl(pyrrolidine-1-carbodi-thio-ato-κS)tin(IV).

In the title compound, [Sn(C6H5)3(C5H8NS2)], the Sn(IV) atom adopts a distorted SnC3S tetra-hedral coordination geometry [spread of bond angles = 94.43 (7)-120.74 (7)°]. A short intra-molecular Sn⋯S contact [3.0270 (9) Å] occurs and two intra-molecular C-H⋯S inter-actions help to establish the conformation. Three of the methyl-ene groups of the pyrrolidine-1-carbodi-thio-ate ligand are disordered over two sets of sites of equal occupancy. In the crystal, very weak C-H⋯S inter-actions link the mol-ecules into a three-dimensional network, with both S atoms acting as acceptors.