Stereo–Chemical Control of Organic Reactions in the Interlamellar Region of Cation–Exchanged Clay Minerals

Carbene intermediates can be generated by thermal, photochemical and transition metal catalysed processes from diazoalkanes. The carbene intermediates are very reactive and can add across double bonds to give 3-membered rings (cyclopropanes), insert into OH bonds to give esters and insert into neighbouring C-H bonds to give 4 or 5-membered rings, such as - and -lactams or lactones. Copper salts and complexes were amongst the first catalysts to be used for carbene generation from diazoalkanes. However, current tendencies are to use very expensive, especially, platinum group salts and complexes to generate the carbene intermediates, as yields and specificity tend to be higher. We have found. On the other hand, that Cu (II) exchanged clay minerals, e.g. Wyoming bentonite, have proven to be very competitive in yield with these transition metal catalysts and they have the added tendency that the restricted reaction space within the clay interlayer favours the more planar/less bulky product when the layer spacing is kept low by judicious choice of solvent. Herein we report a wide range of carbene addition (cyclopropane formation) and C-H insertion reactions (-lactam, -lactam and -lactone formation) catalysed by the Cu(II) exchanged clay minerals and the stereochemical consequences of carrying out the reactions within the clay interlaye

Self-Assembled Lipid Cubic Phase and Cubosomes for the Delivery of Aspirin as a Model Drug

Three-dimensionally organized lipid cubic self-assemblies and derived oil-in-water emulsions called “cubosomes” are attractive for various biotechnological applications due to their ability to be loaded with functional molecules and their associated sustained release properties. Here, we employed both of these lipid-based systems for the delivery of a model drug, aspirin, under comparable conditions. Studies were performed by varying drug-to-lipid ratio and the type of release medium, water and phosphate buffer saline (PBS). Release rates were determined using UV−vis spectroscopy, and small-angle X-ray scattering was used to confirm the type of self-assembled nanostructures formed in these lipid systems. The release from the bulk lipid cubic phase was sustained as compared to that of dispersed cubosomes, and the release in PBS was more efficient than in water. The tortuosity of the architecture, length of the diffusion pathway, type of nanostructure, and physicochemical interaction with the release media evidently contribute to these observations. This work is particularly important as it is the first report where both of these nanostructured lipid systems have been studied together under similar conditions. This work provides important insights into understanding and therefore controlling the release behavior of lipid-based drug nanocarriers

N-Alkylated Linear Heptamethine Polyenes as Potent Non-Azole Leads against Candida Albicans Fungal Infections

In this study, eighteen heptamethine dyes were synthesised and their antifungal activities were evaluated against three clinically relevant yeast species.. The eighteen dyes were placed within classes based on their core subunit i.e. 2,3,3-trimethylindolenine (5a-f), 1,1,2-trimethyl-1H-benzo[e]indole (6a-f), or 2-methylbenzothiazole (7a-f). The results presented herein imply that the three families of cyanine dyes, in particular compounds 5a-f, show high potential as selective scaffolds to treat C. albicans infections. This opens up the opportunity for further optimisation and investigation of this class compounds for potential antifungal treatment

A facile one pot multi component synthesis of alkyl 4-oxo-coumarinyl ethylidene hydrazono-thiazolidin-5-ylidene acetates and their antiviral activity

An efficient one-pot synthesis of alkyl 4-oxo-coumarinyl ethylidene hydrazono-thiazolidin-5-ylidene acetate derivatives has successfully been achieved via a three component cyclization reaction of various substituted 3-acetyl coumarins, thiosemicarbazide and dialkyl acetylenedicarboxylates, in presence of acetic acid. The isolated products were obtained in pure form with high yields through simple workup. The newly synthesised compounds structure was established on the basis of spectral (IR, 1H NMR, 13C NMR, ESI- mass) elemental analysis and single crystal X-ray data. All synthesised compounds were screened for their antiviral activity against a broad spectrum of human viruses in different cell cultures. Of the novel synthesised compounds, thirteen compounds exerted activity against Punta Toro virus, including compound IV-19, for which an antiviral potency was noted against a broad panel of DNA and RNA viruses as well

Electroformation of Particulate Emulsions Using Lamellar and Nonlamellar Lipid Self-Assemblies

We report on the development of an electroformation technique for the preparation of particulate (particle-based) emulsions. These oil-in-water (here, lipid phase acts as an “oil”) emulsions were prepared using nonlamellar lipid phases. Such emulsion particles offer high hydrophobic volumes compared to conventional lipid particles based on lamellar phases (vesicles/liposomes). In addition, the tortuous internal nanostructure contributes through greater surface area per volume of lipid particles allowing an enhanced loading of payloads. The electroformation method makes use of a capacitor formed from two indium tin oxide coated conductive glass surfaces separated by a dielectric aqueous medium. This capacitor setup is enclosed in a custom-designed 3D-printed unit. Lipid molecules, deposited on conductive surfaces, self-assemble into a nanostructure in the presence of an aqueous medium, which when subjected to an alternating current electric field forms nano- and/or microparticles. Optical microscopy, dynamic light scattering, and small-angle X-ray scattering techniques were employed for micro- and nanostructural analyses of electroformed particles. With this method, it is possible to produce particulate emulsions at a very low (e.g., 0.0005 wt % or 0.5 mg/mL) lipid concentration. We demonstrate an applicability of the electroformation method for drug delivery by preparing lipid particles with curcumin, which is a highly important but water-insoluble medicinal compound. As the method employs gentle conditions, it is potentially noninvasive for the delivery of delicate biomolecules and certain drugs, which are prone to decomposition or denaturation due to the high thermomechanical energy input and/or nonaqueous solvents required for existing methods

Antipsoriatic potential of Annona squamosa seed oil: An in-vitro and in-vivo evaluation

Background Corticosteroids remains compound of choice for topical treatment of psoriasis. Several side effects associated with chronic application of corticosteroids limit its uses. Hence, there is a need to find a safe and effective alternative agent for psoriasis treatment. Purpose The study aimed to investigate the in vitro and in vivo efficacy of petroleum ether extract of Annona squamosa seeds (ASO) as an antipsoriatic agent. The toxicity profile of ASO and its effect on psoriasis-induced inflammation has also been determined. Methods Physicochemical characterization was performed to determine constituents of ASO. Anti-proliferative activity of ASO was studied by Sulforhodamine B (SRB) assay using HaCaT cell lines. Oxazolone-induced psoriasis in female Balb/C mice was used as an animal model for investigating in-vivo efficacy of ASO. Inflammatory markers were analyzed by immunohistochemical staining of mice ears. Safety profile of ASO was confirmed by performing acute dose dermal toxicity and repeated dose dermal toxicity testing. Results Predominant presence of polyunsaturated fatty acids viz. linoleic acid and oleic acid in ASO was confirmed by 1H NMR, 13C NMR and GC-MS analysis. The petroleum ether extract of Annona squamosa seeds showed inhibition of cell proliferation of keratinocytes (HaCaT cells). The growth inhibitory property of ASO was significantly higher than that was observed in presence of corticosteroid, clobetasol propionaste (CP). Application of ASO to the ears of Balb/C mice with oxazolone induced psoriasis showed marked reduction in erythema and edema, which was comparable to treatment with 0.05% CP cream. The increased levels of cytokines IL6, IL17, TNF-α, INF-γ, GMCSF, and infiltration of CD4 T cells observed in psoriasis lesions were decreased upon application of ASO. Acute and repeated dermal toxicity studies of ASO did not reveal any adverse events affirming the safety of ASO. Conclusion The present data has demonstrated that ASO is a safe and effective anti-psoriatic agent when tested in animal models. The efficacy of ASO in preclinical studies could further be exploited for the development of potential topical antipsoriatic agent for therapy in human