Structural Changes Induced by Quinones: High-Resolution Microwave Study of 1,4-Naphthoquinone

1,4-Naphthoquinone (1,4-NQ) is an important product of naphthalene oxidation, and it appears as a motif in many biologically active compounds. We have investigated the structure of 1,4-NQ using chirped-pulse Fourier transform microwave spectroscopy and quantum chemistry calculations. The rotational spectra of the parent species, and its ¹³C and ¹⁸O isotopologues were observed in natural abundance, and their spectroscopic parameters were obtained. This allowed the determination of the substitution r_s, mass-weighted r_m and semi-experimental r_e^SE structures of 1,4-NQ. The obtained structural parameters show that the quinone moiety mainly changes the structure of the benzene ring where it is inserted, modifying the C−C bonds to having predominantly single or double bond character. Furthermore, the molecular electrostatic surface potential reveals that the quinone ring becomes electron deficient while the benzene ring remains a nucleophile. The most electrophilic areas are the hydrogens attached to the double bond in the quinone ring. Knowledge of the nucleophilic and electrophilic areas in 1,4-NQ will help understanding its behaviour interacting with other molecules and guide modifications to tune its properties.     

Chemophototherapeutic Ablation of Doxorubicin-Resistant Human Ovarian Tumor Cells†

Porphyrin-phospholipid (PoP) liposomes loaded with Doxorubicin (Dox) have been demonstrated to be an efficient vehicle for chemophototherapy (CPT). Multidrug resistance (MDR) of cancer cells is a problematic phenomenon in which tumor cells develop resistance to chemotherapy. Herein, we report that Dox-resistant tumor cells can be ablated using our previously described formulation termed long-circulating Dox loaded in PoP liposomes (LC-Dox-PoP), which is a PEGylated formulation containing 2 mol. % of the PoP photosensitizer. In vitro studies using free Dox and LC-Dox-PoP showed that human ovarian carcinoma A2780 cells were more susceptible to Dox compared to the corresponding Dox-resistant A2780-R cells. When CPT was applied with LC-Dox-PoP liposomes, effective killing of both nonresistant and resistant A2780 cell lines was observed. An in vivo study to assess the efficiency of LC-Dox-PoP showed effective tumor shrinkage and prolonged survival of athymic nude mice bearing subcutaneous Dox-resistant A2780-R tumor xenografts when they were irradiated with a red laser. Biodistribution analysis demonstrated enhanced tumoral drug uptake in Dox-resistant tumors with CPT, suggesting that increased drug delivery was sufficient to induce ablation of resistant tumor cells.     

Designing Gelatin Based Blood Compatible Materials with Hydrophilic and Hydrophobic Macromolecular Chains

Polymer matrices based on poly 2-hydroxyethyl methacrylate (PHEMA) have emerged as promising materials for developing applications in biomedical and tissue engineering fields. The major criteria of a material to be used as a support matrix in tissue engineering application rests on its biocompatible, hydrophilic, and mechanically strong nature. Although a great deal of research efforts have been put into designing such materials, achieving these properties together for such a material still remains a challenge. Thus, by a judicious combination of natural and synthetic polymers, such as gelatin and copolymers of PHEMA and PAN, respectively, it has been attempted to synthesize a polymer material by redox polymerization method. The prepared polymer matrix was characterized by FTIR, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) techniques. The prepared polymeric biomaterials were assessed for their water sorption potential under varying experimental conditions such as chemical composition, pH, and temperature of the swelling bath. The diffusion mechanism of transport of water molecules arising due to solvent–polymer interaction was analyzed to predict the behavior of continuously relaxing macromolecular chains. The in vitro blood compatibility of the prepared polymeric materials was determined by methods such as blood clot formation, platelet adhesion, percent hemolysis assay, and protein–adsorption on the surface of the prepared biomaterials.     

Synthesis of 14-deoxy-benzylidene-8,17-epoxy-diene-andrographolide derivatives and evaluation of their anticancer activities

Synthesis of 14-deoxy-benzylidene-8,17-epoxy-diene-andrographolide derivatives from andrographolide and evaluation of their anticancer activities were described herein. 3,19 hydroxy groups of andrographolide were protected by benzylidene which undergo m-chloroperbenzoic acid mediated epoxydation in moderate yield to form corresponding epoxy derivatives. Thereafter mild basic condition was applied to perform de-hydroxylation at C-14 which resulted in conjugated diene derivatives of benzylidene epoxy andrographolide. These compounds were examined against different human cancer cell lines and were found to inhibit their proliferation at IC₅₀ in the range of 3–20 μM in order to elucidated the role of allylic hydroxyl group at C-14.     

High-content and high-throughput identification of macrophage polarization phenotypes

Macrophages are plastic cells of the innate immune system that perform a wide range of immune- and homeostasis-related functions. Due to their plasticity, macrophages can polarize into a spectrum of activated phenotypes. Rapid identification of macrophage polarization states provides valuable information for drug discovery, toxicological screening, and immunotherapy evaluation. The complexity associated with macrophage activation limits the ability of current biomarker-based methods to rapidly identify unique activation states. In this study, we demonstrate the ability of a 2-element sensor array that provides an information-rich 5-channel output to successfully determine macrophage polarization phenotypes in a matter of minutes. The simple and robust sensor generates a high dimensional data array which enables accurate macrophage evaluations in standard cell lines and primary cells after cytokine treatment, as well as following exposure to a model disease environment.

Phenotyping macrophage activation states using an array-based sensor. FRET complex assembly selectively interacts with the macrophage surface, generating a fingerprint for each polarization state that is further used to identify the activation state.     

Camphor sulphonic acid mediated quantitative 1,3–diol protection of major Labdane diterpenes isolated from Andrographis paniculata

Phytochemical survey of the methanol extract of the dried aerial parts of Andrographis paniculata led to the isolation of major labdane diterpenes, namely 14-deoxy-11,12-didehydroandrographolide, andrographolide and neoandrographolide. Andrographolide was found to be the major phytoconstituent of the plant which was biologically active. For better physiochemical characteristics and bioefficacy, andrographolide is subjected to semi-synthetic modifications. However, presence of several free hydroxyl groups associated with this molecule make it quite polar and poorly soluble in many organic solvents and hence unsuitable for synthetic modifications. One way of resolving its solubility issue is to protect 1,3-diol quantitatively under mild reaction condition without effecting other functional groups. Reaction conditions were optimised using different solvent systems and catalysts towards this direction. X-ray structure of 3,19-isopropylidene-14-deoxy-11,12-didehydroandrographolide is being reported here for the first time. Isolated compounds and derivatives were confirmed by spectral analysis or X-ray data analysis.     

Perylene-3-ylmethanol: fluorescent organic nanoparticles as a single-component photoresponsive nanocarrier with real-time monitoring of anticancer drug release

We report for the first time the use of perylene-3-ylmethanol fluorescent organic nanoparticles as a drug delivery system. In the present system, perylene-3-ylmethanol nanoparticles performed four important roles: (i) "nanocarriers" for drug delivery; (ii) "phototriggers" for the drug release; (iii) fluorescent chromophores for cell imaging; and (iv) detectors for real time-monitoring of drug release. In vitro biological studies revealed that the newly developed perylene-3-ylmethanol nanoparticles exhibit good biocompatibility and cellular uptake as well as efficient photoregulated anticancer drug release ability. Such fluorescent organic nanoparticles may open up new perspectives for designing a new class of promising photoresponsive nanocarriers for drug delivery.