Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight.

Polyanhydrides have been synthesized for decades by melt-polycondensation of diacid monomers and 5 to >10 times mole excess acetic anhydride to diacid monomers to form polymers with a polydispersity ranging from 2.5 to 6 and low reproducibility. Hydrophobic segments in polyanhydrides are beneficial to hinder the characteristic hydrolytic cleavage of an anhydride bond that provides stable polyanhydrides at room temperature. The objective of this work is to synthesize aliphatic polyanhydrides with various hydrophobic segments, controllable and reproducible molecular weight, and low polydispersity that are essential for potential use as drug carriers. A series of polyanhydrides of suberic, azelaic, sebacic, and dodecanedioic acids with controlled molecular weight, reduced polydispersity, and standard deviation of molecular weights, have been synthesized. All synthesized polyanhydrides were thoroughly characterized by NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography. Molecular weights of the synthesized polyanhydrides are highly controllable, depending on the degree of activation of the dicarboxylic acid monomers, i.e., the amount of acetic anhydride used during synthesis. Polyanhydrides have been synthesized in triplicate by melt-polycondensation, using various mole ratios of acetic anhydride to diacids. The standard deviation of the molecular weights of the polyanhydrides is minute when using 1 equivalent of acetic anhydride during the activation of dicarboxylic acids, whereas if excess acetic anhydride is used, the standard deviation is very high. The effect of safe and natural inorganic catalysts, Calcium oxide, Zinc oxide, and Calcium carbonate on polymerization is also studied. As-synthesized poly(sebacic acid) can offer convenience to use in controlled drug delivery applications. In vitro drug release study using Temozolamide (TMZ), a medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma, shows 14% TMZ release after the first hour and 70% release over one day from the poly(sebacic acid) wafers.

Unprecedented formation of palladium(II)-pyrazole based thiourea from chromone thiosemicarbazone and [PdCl2(PPh3)2]: Interaction with biomolecules and apoptosis through mitochondrial signaling pathway.

Two novel pyrazole based thiourea palladium(II) complexes, [PdCl(PPh3)(C9H8NO2S-pz)] (1) and [PdCl(PPh3)(C14H10NO2S-pz)] (2) [pz = pyrazole (C3H2N2)] have been obtained unexpectedly from chromone thiosemicarbazones (L1 and L2) and [PdCl2(PPh3)2]. The compounds have been fully characterized by physicochemical studies. The single crystal X-ray diffraction and spectral studies revealed square planar geometry for the complexes. The conversion of chromone thiosemicarbazone into pyrazole based thiourea might have happened through coordination to palladium(II) ion after enolization, Michael addition and ring opening followed by cyclization. To the best of our knowledge, this is the first report for the conversion of chromone thiosemicarbazone into pyrazole based thiourea moiety. Plausible mechanism was proposed based on the spectroscopic studies. Calf thymus (CT) DNA binding of the compounds was explored using various spectroscopic and molecular docking methods. DNA cleavage studies suggested that complexes 1 and 2 had the capacity to cleave the supercoiled DNA (pUC19) to its naked form. In vitro cytotoxic property of the ligands and complexes has been evaluated against three human cancer cells such as A549, HepG-2 and U937. Complex 2 exhibited potent cytotoxic activity against HepG-2 cells with the IC50 value of 10.4 µM. In addition, mechanistic studies showed that complex 2 induced apoptosis through mitochondrial signaling pathway in HepG-2 cells. Beneficially, complex 2 showed less toxicity against human lung (IMR90) normal cells and hence it emerges as a potential candidate for further studies.

A New Class of ß-Pyrrolidino-1,2,3-Triazole Derivatives as ß-Adrenergic Receptor Inhibitors: Synthesis, Pharmacological, and Docking Studies.

New 1,4-disubstituted ß-pyrrolidino-1,2,3-triazoles were synthesized using a reusable copper-iodide-doped neutral alumina catalyst. Synthesis of diversely substituted triazoles and recyclability of CuI catalyst explains the broad scope of this protocol. The synthesized compounds were screened for their antimicrobial and anticancer properties. Most of the compounds showed significant antimicrobial activities against all the tested microorganisms compared to standard drugs. Furthermore, compounds 5a, 5e, 5g, 5h, 5i, and 5j showed moderate to potent activities against A549 and HepG-2 cells. In addition, compounds 5g and 5h displayed potential cytotoxicity activity against A549 cells with IC50 values of 72 ± 3.21 and 58 ± 2.31 µM, respectively. The molecular docking study revealed that some of the synthesized compounds exhibited comparable binding as co-crystalized ligands with the DNA topoisomerase IV and anaplastic lymphoma kinase receptors.

Ru(II)-Catalyzed Regiospecific C-H/O-H Oxidative Annulation to Access Isochromeno[8,1-ab]phenazines: Far-Red Fluorescence and Live Cancer Cell Imaging.

A facile ruthenium(II)-catalyzed regiospecific C-H/O-H oxidative annulation methodology was developed to construct isochromeno[8,1-ab]phenazines. This methodology delivers various advantages, such as scope for diverse substrates, tolerance to a range of functional groups, stability under air, and yields regioselective products. This methodology was successfully applied to synthesize far red (FR) fluorescent probes for live cancer cell imaging. The synthesized compounds displayed notable fluorescence properties in solution and thin-film. Their application in live cancer cell imaging was investigated using various cancer cell lines. The synthesized compound showed prominent FR fluorescence, with high quantum yield, and exhibited better cell-imaging properties, with excellent biocompatibility.

Synthesis of Ni(II) complexes bearing indole-based thiosemicarbazone ligands for interaction with biomolecules and some biological applications.

A series of new Ni(II) complexes containing indole-based thiosemicarbazone ligands was synthesized and characterized by elemental analyses, and UV-visible, FT-IR, 1H & 13C NMR and mass spectroscopic techniques. The Ni(II) complexes (1-4) bear the general formula [Ni{C10H9N2NHCSNH(R)}2] where R = hydrogen (1), 4-methyl (2), 4-phenyl (3) and 4-cyclohexyl (4). Molecular structure of ligands (L3 and L4) and complexes (2, 3 and 4) was confirmed by single crystal X-ray crystallography. Four coordinated Ni(II) complexes showed square planar geometry. The interaction of the Ni(II) complexes with calf thymus DNA (CT-DNA) has been evaluated by absorption spectroscopic and ethidium bromide (EB) competitive binding studies, which revealed the intercalative interaction of the complexes with CT-DNA. Gel electrophoresis experiments showed the cleavage of DNA by the complexes without any external agent. Further, the interaction of the complexes with bovine serum albumin (BSA) was investigated using UV-visible, fluorescence and synchronous fluorescence spectroscopic methods, which showed that the complexes could bind strongly with BSA. Molecular docking was employed to understand the binding of the Ni(II) complexes with the molecular target B-DNA, human DNA topoisomerase I and BSA. All the Ni(II) complexes possess high antioxidant activity against 2-2-diphenyl-1-picrylhydrazyl (DPPH) radical and antihaemolytic activity. In addition, in vitro cytotoxicity of the Ni(II) complexes against lung cancer (A549), human breast cancer (MCF7) and mouse embryonic fibroblasts (L929) cell lines was investigated. Complex 4 has high cytotoxicity. The mode of cell death effected by complex 4 has been explored using Hoechst 33258 staining. Nickel(II) complexes of thiosemicarbazone ligands were synthesized and their DNA/protein binding, DNA cleavage and cytotoxicity abilities were studied.

Isolation and characterization of 2-hydroxy-9,10-anthraquinone from Streptomyces olivochromogenes (ERINLG-261) with antimicrobial and antiproliferative properties

Abstract Currently Streptomyces is one of the most important antibiotic producing microorganisms against several diseases. In the present study Streptomyces olivochromogenes ERINLG-261 was isolated from the soil samples of the Mudumalai hills, Western Ghats, India. Morphological, physiological, biochemical and 16S rRNA studies strongly suggested that this isolate belonged to the genus Streptomyces. ERINLG-261 showed good antimicrobial activity against different bacteria and fungi in Micromonospora fermentation medium. The active ethyl acetate extract was packed in column chromatography over silica gel which led to the isolation of 2-hydroxy-9,10-anthraquinone as the active principle. The isolated compound showed good antimicrobial activity against tested bacteria and fungi in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) studies. The compound showed moderate in vitro antiproliferative activity against A549 and COLO320 cells. The compound was subjected to molecular docking studies for the inhibition of Topoisomerase, TtgR and Beta-lactamase enzymes which are targets for antimicrobials. Docking results of the compound showed low docking energy with these enzymes indicating its usefulness as antimicrobial agent. This is the first report of antimicrobial and antiproliferative activity of 2-hydroxy-9,10-anthraquinone isolated from Streptomyces olivochromogenes along with molecular docking studies.

Synthesis of cinnolines via Rh(iii)-catalysed dehydrogenative C-H/N-H functionalization: aggregation induced emission and cell imaging.

Rhodium catalysed dehydrogenative C-H/N-H functionalization was developed to construct phthalazino[2,3-a]-/indazolo[1,2-a]cinnolines by reacting N-phenyl phthalazine/indazole with alkynes. The synthesized compounds exhibit prominent fluorescence properties in solid and aggregation states. Their application in cell imaging was investigated using various cancer cell lines.