A Simple and Efficient Synthesis of 4-Arylacridinediones and 6-Aryldiindeno[1,2-b:2,1-e]pyridinediones using CuI Nanoparticles as Catalyst under Solvent-Free Conditions.

AIMS AND OBJECTIVES: The importance of acridine core structure and other heterocycles containing its framework is well known, as they are found in numerous compounds with a variety of biological effects. Pyridine is also an important solvent and heterocyclic nucleus for the design and synthesis of novel molecules with biological properties. It occurs in several natural compounds which are used as a precursor in agrochemicals and pharmaceuticals. The utility of nanostructured metal salts because of their small size and high surface area as catalysts in organic synthesis has drawn special attention due to their better properties such as slower reaction rate, reusability of the catalyst, and higher yields of products compared to the bulk size. Nanosized copper iodide is one reusable Lewis acid catalyst which has revealed several catalytic activities for the synthesis of organic compounds and others. As part of our recent study to develop heterocyclic syntheses using nanostructured catalysts, we now report an efficient and clean synthetic route to 4-arylacridinediones and 6-aryldiindeno[1,2-b:2,1-e]pyridinediones via a condensation reaction catalyzed by CuI nanoparticles under solvent-free conditions. MATERIALS AND METHODS: The present work deals with the condensation reaction of aromatic aldehydes, ammonium acetate and active methylene compounds comprising dimedone or 1,3- indanedione in the presence of a catalytic amount of the synthesized CuI nanoparticles could be applied for the solvent-free preparation of 4-arylacridinediones and 6-aryldiindeno[1,2-b:2,1- e]pyridinediones at 70 °C within 60 min. RESULTS: A series of 9-aryl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinediones and 6-aryldiindeno[1,2-b:2,1-e]pyridine-5,7-diones were synthesized in high to excellent yields via a simple one-pot three-component coupling reaction using the synthesized CuI nanoparticles as an efficient and recyclable catalyst. All synthesized compounds were well characterized by their satisfactory elemental analyses, IR, 1H and 13C NMR spectroscopy. The synthesized catalyst was fully characterized by XRD, TEM and SEM techniques. CONCLUSION: A solvent-free condensation between aromatic aldehydes, ammonium acetate and active methylene compounds comprising dimedone or 1,3-indanedione, in the presence of CuI nanoparticles as an efficient and recyclable catalyst leads to the formation of 4-arylacridinediones and 6-aryldiindeno[1,2-b:2,1-e]pyridinediones. This novel and practical approach has a number of advantages for instance, the condensation itself is solvent-free, the total amount of solvent used in the whole process is significantly decreased, the yields of pure products are high to excellent without any by-products, the catalyst is reusable, and the work-up is very simple.

Determination of Bortezomib in API Samples Using HPLC: Assessment of Enantiomeric and Diastereomeric Impurities.

A new, normal phase high performance liquid chromatography (NP-HPLC) method was developed for separation of Bortezomib (BZB) enantiomers and quantitative determination of (1S,2R)-enantiomer of BZB in active pharmaceutical ingredient (API) samples. The developed method was validated based on International Conference on Harmonisation (ICH) guidelines and it was proved to be accurate, precise and robust. The obtained resolution (RS) between the enantiomers was more than 2. The calibration curve for (1S,2R)-enantiomer was found to be linear in the concentration range of 0.24-5.36 mg/L with regression coefficient (R2) of 0.9998. Additionally, the limit of detection (LOD) and limit of quantification (LOQ) were 0.052 and 0.16 mg/L, respectively. Also, in this study, a precise, sensitive and robust gradient reversed-phase HPLC (RP-HPLC) method was developed and validated for determination of BZB in API samples. The detector response was linear over the concentration range of 0.26-1110.5 mg/L. The values of R2, LOD and LOQ were 0.9999, 0.084 and 0.25 mg/L, respectively. For both NP-HPLC and RP-HPLC methods, all of the RSD (%) values obtained in the precision study were <1.0%. System suitability parameters in terms of tailing factor (TF), number of theoretical plates (N) and RS were TF < 2.0, N > 2,000 and RS > 2.0. The performance of two common integration methods of valley to valley and drop perpendicular for drawing the baseline between two adjacent peaks were investigated for the determination of diastereomeric impurity (Imp-D) in the BZB-API samples. The results showed that the valley to valley method outperform the drop perpendicular method for calculation of Imp-D peak areas. Therefore, valley to valley method was chosen for peak integration.

Sustained release Curcumin loaded Solid Lipid Nanoparticles.

PURPOSE: curcumin is poorly water soluble drug with low bioavailability. Use of lipid systems in lipophilic substances increases solubility and bioavailability of poorly soluble drugs. The aim of this study was to prepare curcumin loaded Solid Lipid Nanoparticles (SLNs) with high loading efficiency, small particle size and prolonged release profile with enhanced antibacterial efficacy. METHODS: to synthesize stable SLNs, freeze- Drying was done using mannitol as cryoprotectant. Cholesterol was used as carrier because of good tolerability and biocompatibility. SLNs were prepared using high pressure homogenization method. RESULTS: optimized SLNs had 112 and 163 nm particle size before and after freeze drying, respectively. The prepared SLNs had 71% loading efficiency. 90% of loaded curcumin was released after 48 hours. Morphologic study for formulation was done by taking SEM pictures of curcumin SLNs. RESULTS show the spherical shape of curcumin SLNs. DSC studies were performed to determine prolonged release mechanism. Antimicrobial studies were done to compare the antimicrobial efficacy of curcumin SLNs with free curcumin. DSC studies showed probability of formation of hydrogen bonds between cholesterol and curcumin which resulted in prolonged release of curcumin. Lipid structure of cholesterol could cause enhanced permeability in studied bacteria to increase antibacterial characteristics of curcumin. CONCLUSION: the designed curcumin SLNs could be candidate for formulation of different dosage forms or cosmeceutical products.

Synthesis of novel Gn-RH analogues using Ugi-4MCR.

An efficient method for the synthesis of some Gn-RH analogues based on Ugi reaction has been developed. Four-component reaction of N- and C-terminus peptides, aromatic aldehydes and isocyanides affords novel Gn-RH analogues derived from triptorelin and gonadorelin. All of the products were purified using preparative HPLC and the structures were assigned according to MALDI-mass spectrometry data.