Biological Activity of Quinazolinones

The chemical structure of quinazolinones includes benzene ring fused with 2-pyrimidinone (1), 4-pyrimidinone (2) or 2,4-pyrimidinedione (3) ring, and are named as quinazolin-2(1H)-one, quinazolin-4(3H)-one or quinazolin-2,4(1H, 3H)-one, respectively. The chemical structure of quinazolinones constitutes a crucial scaffold of natural and synthetic compounds with various therapeutic and biological activities. Quinazolinones are first synthesized by Stefan Niementowski (1866–1925) and named after Niementowski quinazolinone synthesis. Quinazolinones have strongly attracted the interest of medicinal chemist as they constitute a large class of compounds that exhibited broad spectrum of biological activities including antimicrobial, antimalarial, anticonvulsant, anticancer, antileishmanial, anti-inflammatory, etc. This chapter provides a brief overview on the recent advances on chemical and pharmacological aspects of quinazolinone derivatives published in the last decade

Molecular scaffold and biological activities of anti- Alzheimer agents

Alzheimer’s disease (AD) is an age-associated and neurodegenerative illness which results in progressive dementia and severe cognitive malfunctions. The pathogenesis of AD is affected by some factors such as accumulation of β-amyloid, aggregation of tau protein, cholinergic insufficiency, neuroinflammation, oxidative stress and apoptosis. Factors such as gene mutation, as well as environmental, psychical and other co-existing diseases influence the pathogenesis of AD to varying extents. While there are no available drugs for arresting AD-associated neurodegeneration, the characteristics that result from AD treatment are considered as indexes of symptomatic cure. Several medications with varied scaffolds have been used for the treatment of many cognitive syndromes, including AD. These medications act as anti-inflammatory and antioxidant agents, and as inhibitors of cholinesterase and β-secretase. Moreover, these drugs suppress the accumulation of β-amyloid and its fibril. This review is an update and compilation of various scaffolds of anti-AD medications used to ameliorate the deleterious effects of the disease, based on their pharmacologic characteristics

Development and validation of a UPLC method for quantification of antiviral agent, Acyclovir in lipid-based formulations

AbstractPurposeThe objective of the current study is to evaluate the Ultra Performance Liquid Chromatography (UPLC) method for quantification of Acyclovir in lipid-based formulations.MethodA simple, rapid, reliable and precise reversed phase UPLC method has been developed and validated according to the regulatory guidelines, which composed of isocratic mobile phase; 0.25% formic acid (FA) in Milli-Q water with a flow rate of 0.5ml/min, and column BEH C18 (2.1×50mm, 1.7μm). The detection was carried out at 254nm.ResultsThe developed UPLC method was found to be rapid (1.2min run time), selective with well resoluted Acyclovir peak (0.89min) from different lipid matrices and sensitive (Limit of Detection (LOD) was 0.3ppm and Lower Limit of Quantification (LLOQ) was 1ppm). The accuracy and precision were determined and were perfectly matching with the standard FDA limits.ConclusionThe study showed that the proposed UPLC method can be used for the assessment of drug purity, stability, solubility and lipid-formulation release profile with no interference of excipients or related substances of active pharmaceutical ingredient

Erythrocyte nanovesicles: Biogenesis, biological roles and therapeutic approach Erythrocyte nanovesicles

AbstractNanovesicles (NVs) represent a novel transporter for cell signals to modify functions of target cells. Therefore, NVs play many roles in both physiological and pathological processes. This report highlights biogenesis, composition and biological roles of erythrocytes derived nanovesicles (EDNVs). Furthermore, we address utilization of EDNVs as novel drug delivery cargo as well as therapeutic target. EDNVs are lipid bilayer vesicles rich in phospholipids, proteins, lipid raft, and hemoglobin. In vivo EDNVs biogenesis is triggered by an increase of intracellular calcium levels, ATP depletion and under effect of oxidative stress conditions. However, in vitro production of EDNVs can be achieved via hypotonic treatment and extrusion of erythrocyte. NVs can be used as biomarkers for diagnosis, monitoring of therapy and drug delivery system. Many therapeutic agents are suggested to decrease NVs biogenesis

Plackett–Burman randomization method for Bacterial Ghosts preparation form E. coli JM109

AbstractPlackett–Burman randomization method is a conventional tool for variables randomization aiming at optimization. Bacterial Ghosts (BGs) preparation has been recently established using methods other than the E lysis gene. The protocol has been based mainly on using critical concentrations from chemical compounds able to convert viable cells to BGs. The Minimum Inhibition Concentration (MIC) and the Minimum Growth Concentration (MGC) were the main guide for the BGs preparation. In this study, Escherichia coli JM109 DEC has been used to produce the BGs following the original protocol. The study contained a detail protocol for BGs preparation that could be used as a guide

Solubility of Gliclazide in Transcutol + Water Co-solvent Mixtures at (298.15 to 333.15) K

The aim of present investigation was to determine the mole fraction solubility of a poorly water soluble antidiabetic drug gliclazide (GLZ) in mono-solvents and various Transcutol + water co-solvent mixtures at (298.15 to 333.15) K. The experimental solubility of GLZ was measured by shake flask method and resulting data was correlated with the modified Apelblat model at each temperature studied. Good correlation was observed between the experimental data of GLZ and calculated one with absolute relative deviation in the range of (0.050 to 5.680) %. The correlation coefficients were observed in the range of 0.9966 to 0.9995 which indicated good fitting of experimental solubility data. The lowest mole fraction solubility of GLZ was observed in pure water (1.9 × 10–6 at 298.15 K) whereas the highest one was observed in pure Transcutol (11.9 × 10–3 at 298.15 K). The enthalpies and entropies for GLZ dissolution were observed as positive values in the range of (15.742 to 40.551) kJ mol–1 and (52.801 to 121.721) J mol–1 K–1, respectively in all sample matrices. These results of thermodynamic parameters indicated that the dissolution of GLZ is endothermic and an entropy-driven process. Based on current solubility data, GLZ was considered as practically insoluble (poorly soluble) in pure water and soluble in Transcutol. These preliminary studies indicated that Transcutol could be used as a co-solvent for solubility enhancement of GLZ which could help in preformulation studies and formulation development of GLZ

Sponge-Like: A New Protocol for Preparing Bacterial Ghosts

Bacterial Ghosts (BGs) received an increasing interest in the recent years for their promising medicinal and pharmaceutical applications. In this study, for the first time we introduce a new protocol for BGs production. E. coli BL21 (DE3) pLysS (Promega) was used as a model to establish a general protocol for BGs preparation. The protocol is based on using active chemical compounds in concentrations less than the Minimum Inhibition Concentration (MIC). Those chemical compounds are SDS, NaOH, and H2O2. Plackett-Burman experimental design was used to map the best conditions for BGs production. Normal and electronic microscopes were used to evaluate the BGs quality (BGQ). Spectrophotometer was used to evaluate the amount of the released protein and DNA. Agarose gel electrophoresis was used to determine the existence of any residue of DNA after each BGs preparation. Viable cells, which existed after running this protocol, were subjected to lysis by inducing the lysozyme gene carried on pLysS plasmid. This protocol is able to produce BGs that can be used in different biotechnological applications

Influence of pravastatin chitosan nanoparticles on erythrocytes cholesterol and redox homeostasis: An in vitro study

AbstractThe objective of this study was to develop and characterize chitosan nanoparticles (CSNPs) to increase efficacy of pravastatin (PR) on erythrocytes redox status. CSNPs and PR loaded CSNPs (PRCSNPs) were prepared by ionic gelation method. The particle size, zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) and X-ray diffraction (XRD) were used to investigate physicochemical characters of the prepared nanoparticles. The present results revealed that CSNPs and PRCSNPs have nanosize about 90nm with spherical shape, positive zeta potential and prolonged PR release. Moreover, DSC and FTIR indicated no chemical interactions between PR and CS. In vitro studies revealed that, erythrocyte uptake of PR from PRCSNPs was higher than free PR solution. Incubation of erythrocytes in high cholesterol plasma, hypercholesterolemia (HC), increases membrane cholesterol, erythrocyte hemolysis, oxidized glutathione (GSH), protein carbonyl (PCC), and malondialdeyhe (MDA). However, HC significantly decreases PR uptake by erythrocytes, superoxide dismutase (SOD), glutathione peroxidase (GPx) catalase (CAT) activities, reduced GSH and nitrite levels compared to control. By contrast, treatment of HC with PR plus CS as free drug or nanostructure formula keeps the measured parameters at values near that of control. The effect of CSNPs and PRCSNPs on redox status of erythrocytes was more prominent than free drugs. In conclusion, PRCSNPs are promising drug carrier to deliver PR into erythrocytes, moreover, PRCSNPs possess promising characteristics with high biological safety for treatment of HC induced disruption of redox homeostasis

Stability assessment of cinnarizine in self-emulsifying drug delivery systems

The current study was designed to evaluate the chemical and physical stability of cinnarizine within self-emulsifying drug delivery systems. According to International Conference of Harmonization guidelines, the selected formulations were enrolled into both accelerated and long-term stability studies up to 6 and 12 months, respectively. The chemical stability of the formulations was assessed periodically based on the intact cinnarizine level. The physical stability was evaluated based on the physical appearance and color change pattern of the formulations. The accelerated stability study revealed significant cinnarizine degradation in all the tested formulations at 3 and 6 months. All the tested formulations experienced sharp discoloration within 6 months of storage. On the other hand, the long-term stability study showed no significant cinnarizine degradation or color change within the formulations containing 100 % saturated medium chain glycerides (as oil component). While, the formulations containing 50 % unsaturated long chain fatty acids showed considerable drug degradation as well as significant discoloration. Accordingly, The formulations containing 100 % saturated medium chain glycerides provide excellent chemical and physical stability pattern and have the potential to provide a stable dosage form of cinnarizine.Colegio de Farmacéuticos de la Provincia de Buenos Aire