Crystal Engineering: A Powerful Tool towards Designing Pharmaceutical Solids with Desirable Physicochemical Properties

Nowadays various techniques have been applied for the improvement of physicochemical properties such as solubility, bioavailability, stability and hygroscopic nature of pharmaceutical solids without effecting the biochemical composition of the active pharmaceutical ingredients (API). Supramolecular approach specially the crystal engineering technique is one of the best techniques which play an important role to improve the physico-chemical, thermal and mechanical properties of drug molecules. Crystal engineering approach offers a number of routes such as co-crystallization, polymorphism, hydrate and salt formation with the help of which drug molecules with good physico-chemical behavior can be prepared. This article covers the concept of supramolecular chemistry and crystal engineering approach for the preparation of co-crystals and their application in pharmaceutical industries

Hydride pinning pathway in the hydrogenation of CO2 into formic acid on dimeric tin dioxide

Capture of CO2 and its conversion into organic feedstocks are increasingly needed as society moves towards a renewable energy economy. Here, a hydride‐assisted selective reduction pathway is proposed for the conversion of CO2 to formic acid (FA) over SnO2 monomers and dimers. Our density functional theory calculations infer a strong chemisorption of CO2 on SnO2 clusters forming a carbonate structure, whereas heterolytic cleavage of H2 provides a new pathway for the selective reduction of CO2 to formic acid at low overpotential. Among the two investigated pathways for reduction of CO2 to HCOOH, the hydride pinning pathway is found promising with a unique selectivity for HCOOH. The negatively‐charged hydride forms on the cluster during the dissociation of H2 and facilitates the formation of a formate intermediate, which determines the selectivity for FA over the alternative CO and H2 evolution reaction. It is confirmed that SnO2 clusters exhibit a different catalytic behaviour from their surface equivalents, thus offering promise for future work investigating the reduction of CO2 to FA via a hydride pinning pathway at low overpotential and CO2 capturing

Green synthesized silver nanoparticles destroy multidrug resistant bacteria via reactive oxygen species mediated membrane damage

AbstractThe growing need of antimicrobial agent for novel therapies against multi-drug resistant bacteria has drawn researchers to green nanotechnology. Especially, eco-friendly biosynthesis of silver nanoparticles (Ag NPs) has shown its interesting impact against bacterial infection in laboratory research. In this study, a simple method was developed to form Ag NPs at room temperature, bio-reduction of silver ions from silver nitrate salt by leaf extract from Ocimum gratissimum. The Ag NPs appear to be capped with plant proteins, but are otherwise highly crystalline and pure. The Ag NPs have a zeta potential of −15mV, a hydrodynamic diameter of 31nm with polydispersity index of 0.65, and dry sizes of 18±3nm and 16±2nm, based on scanning and transmission electron microscopy respectively. The minimum inhibitory concentration (MIC) of the Ag NPs against a multi-drug resistant Escherichia coli was 4μg/mL and the minimum bactericidal concentration (MBC) was 8μg/mL, while the MIC and MBC against a resistant strain of Staphylococcus aureus were slightly higher at 8μg/mL and 16μg/mL respectively. Further, the Ag NPs inhibited biofilm formation by both Escherichia coli and S. aureus at concentrations similar to the MIC for each strain. Treatment of E. coli and S. aureus with Ag NPs resulted in damage to the surface of the cells and the production of reactive oxygen species. Both mechanisms likely contribute to bacterial cell death. In summary, this new method appears promising for green biosynthesis of pure Ag NPs with potent antimicrobial activity

Assessment of chalcones as cancer chemopreventive agents

Chemoprevention is based upon the use of natural or synthetic products to eliminate or minimize the development of cancer1. Many cancers are thought to occur due to processes such as oxidative stress and lipid peroxidation causing DNA damage. Chemopreventive compounds may prevent such damage from occurring. Chalcones belong to the flavonoid based group of compounds and have been reported to possess cancer chemopreventive properties2,3. In this study, we investigated the ability of novel synthetic chalcones to act as chemopreventive agents. The aim was to assess the ability of the chalcones to switch on the transcription factor Nrf2 thus inducing many cell defence genes. This was achieved using the AREc32 reporter cell line that contains the luciferase gene linked to the antioxidant response element (ARE), which is a sequence found within the promoters of cell defence genes to which the Nrf2 transcription factor binds4. The luciferase reporter AREc32 cell line was exposed to varying concentrations of synthetic chalcones to determine a suitable non-toxic concentration to use (MTT assay). The AREc32 cells were then exposed to this non-toxic concentration of chalcones for 24 h after which the amount of luciferase activity (Nrf2 activity) was quantified. Of the 30 chalcones tested, 12 chalcones were found to activate the luciferase reporter gene by 2-fold or more (relative to untreated control) with the greatest induction being 16-fold. Further investigations are now in progress to delineate the common structural features of the chalcones that give the greatest induction in addition to the ability of these chalcones to prevent cellular cytotoxicity

Population distribution analyses reveal a hierarchy of molecular players underlying parallel endocytic pathways.

Single-cell-resolved measurements reveal heterogeneous distributions of clathrin-dependent (CD) and -independent (CLIC/GEEC: CG) endocytic activity in Drosophila cell populations. dsRNA-mediated knockdown of core versus peripheral endocytic machinery induces strong changes in the mean, or subtle changes in the shapes of these distributions, respectively. By quantifying these subtle shape changes for 27 single-cell features which report on endocytic activity and cell morphology, we organize 1072 Drosophila genes into a tree-like hierarchy. We find that tree nodes contain gene sets enriched in functional classes and protein complexes, providing a portrait of core and peripheral control of CD and CG endocytosis. For 470 genes we obtain additional features from separate assays and classify them into early- or late-acting genes of the endocytic pathways. Detailed analyses of specific genes at intermediate levels of the tree suggest that Vacuolar ATPase and lysosomal genes involved in vacuolar biogenesis play an evolutionarily conserved role in CG endocytosis

Cytotoxic stilbenes and canthinone alkaloids from Brucea antidysenterica (Simaroubaceae)

Phytochemical study of the root and bark of Brucea antidysenterica J. F. Mill. (Simaroubaceae) afforded three new compounds including a stilbene glycoside bruceanoside A (1), and two canthinone alkaloids bruceacanthinones A (3) and B (4), as well as ten known secondary metabolites, rhaponticin (2), 1,11-dimethoxycanthin-6-one (5), canthin-6-one (6), 1-methoxycanthin-6-one (7), 2-methoxycanthin-6-one (8), 2-hydroxy-1,11-dimethoxycanthin-6-one (9), β-carboline-1-propionic acid (10), cleomiscosin C (11), cleomiscosin A (12) and hydnocarpin (13). The structures of all the compounds were determined using spectrometric and spectroscopic methods including 1D and 2D NMR, and HRSEIMS. The identity of the known compounds was further confirmed by comparison of their data with those reported in the literature. The root and bark methanolic extracts, the dichloromethane and ethyl acetate soluble fractions, as well as the isolated compounds (3–13), were assessed for their cytotoxicity against the cancer cell lines A-549, MCF-7 and PC-3. The results suggested that compounds in the extracts might possess a synergic action in their cytotoxicity

Beilschglabrines A and B: Two new bioactive phenanthrene alkaloids from the stem bark of Beilschmiedia glabra

Two new phenanthrene alkaloids, beilschglabrines A (1) and B (2) were isolated from the stem bark of Beilschmiedia glabra, together with lupeol, taraxerol, and 24-methylenelanosta-7,9-diene-3β-15α-diol. The structures of the isolated compounds were elucidated by extensive spectroscopic data analysis and comparison with respective literature data. The compounds were tested for DPPH radical scavenging, acetylcholinesterase and lipoxygenase inhibitory activities. Compound 1 displayed considerable activity in the acetylcholinesterase (IC50 50.4 μM), the DPPH radical scavenging (IC50 115.9 μM) and the lipoxygenase (IC50 32.8 μM) assays. © 2016 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved