Medicinal Chemistry - Volume 8, Issue 4, 2012

Selective chemical functionalization of cyclodextrins (CDs) is a readily amenable methodology to produce amphiphilic macromolecules endowed with modulable self-organizing capabilities. Herein, the synthesis of well-defined amphiphilic CD derivatives, with a “skirt-type” architecture, that incorporate long-chain fatty esters at the secondary hydroxyl rim and a variety of chemical functionalities (e. g. iodo, bromo, azido, cyst Read More

In the present work, a promising formulation of an inhaled powder based on tobramycin-loaded microparticles has been reported. Biodegradable microparticles with controlled diameters in the range of 1-5 μm and narrow size distribution were synthesized by Flow Focusing® technology. Particles production was planned and optimized with the aid of a well-established mathematic model. Close agreements between theore Read More

Lipid nanoparticles loading the sunscreen 2,4-dihydroxybenzophenone (DHB-LNPs) have been prepared by high-pressure homogenization and ultrasound techniques. The combination of both methodologies improves the entrapment efficiency percentage reaching 95%. The morphology of the DHB-LNPs was studied with scanning electron microscopy (SEM) and atomic force microscopy (AFM), while the surface and interior c Read More

Calcium is essential to homeostasis and functioning of multiple organ systems. Its circulating concentration is maintained within a very tight physiologic range: 2.25 and 2.50 mmol/L. Under physiological conditions, the ionized calcium concentration is regulated by the parathyroid hormone (PTH), and 1,25(OH)2 vitamin D through interactions on target organs such as kidney, bone and intestine. In mild, moderate, a Read More

Hypercalcemia is a relatively frequent alteration, mostly associated to primary hyperparathyroidism (PHPT) and malignancy-associated hypercalcemia (MAH). Treatment first includes rehydration and loop diuretics, as general measures. Bisphosphonates are considered the drugs of choice due to their long-term management. Calcitonin is preferable in the short-term control of severe hypercalcemia. The antireabsorp Read More

Acute hypercalcemia is a life-threatening rather rare condition. This condition may represent an acute decompensation of a pre-existing hypercalcemia, or may be acute at the first instance of the electrolyte disturbance. Hypercalcemic patients can present with a broad spectrum of symptoms, but most of them are mild and non-specific. Hypercalcemia affects a group of organs, which are considered together as a sy Read More

The synthesis of 4-(1-adamantyl)-4,4-diarylbutylamines 1, 5-(1-adamantyl)-5,5-diarylpentylamines 2 and 6-(1-adamantyl)-6,6-diarylhexylamines 3 is described and the σ1, σ2-receptors and sodium channels binding affinity of compounds 1 were investigated. The in vitro activity of compounds 1, 2 and 3 against main cancer cell lines is significant. One of the most active analogs, 1a, had an interesting in vivo anticancer profile agains Read More

In order to develop a new series of dual inhibitors of SRC and ABL, and to investigate whether the pyrimidin- 4-ylamino moiety is critical for dasatinib’s activity, acetyl substitution was adopted as alternate scaffold at the 2-amino group. Eighteen novel dasatinib derivatives were developed by a parallel synthesis approach and evaluated for their antiproliferative effects. Preliminary tests showed that some of the target comp Read More

In this study, the novel germatrane compound, 3-(2, 8, 9-trioxa-5-aza-1- germatricyclo [3.3.3.0] undecane-1- yl)-3-(4-hydroxy-3- methoxyphenyl)-propionic acid (1), has been synthesized and its activities against cervical tumor U14 were evaluated in vitro and in vivo. The results have demonstrated that the compound posed significant inhibition on U14 tumor with IC50 values of 48.57 mg/L in cell-based assay and tumo Read More

A set of thirty one substituted 2-phenoxy-N-phenylacetamide derivatives with HIF-1 inhibitory activities was subjected to 2D and 3D Quantitative Structure Activity Relationship (QSAR) studies using various combinations of descriptors. 2D-QSAR was performed using Multiple Linear Regression (MLR), Principal Component Regression (PCR) and Partial Least Squares Regression (PLS) methods. Among these three methods Multiple Read More

Modern chemotherapy is interested in developing new agents with high efficiency of treatment in low-dose medication strategies, lower side toxicity and stronger specificity to the tumor cells. Vanadocene dichloride (VDC) belongs to the group of the most promising metallocene antitumor agents; however, its mechanism of action and cytotoxicity profile are not fully understood. In this paper we assess cytotoxic effects of V Read More

In order to reduce toxicity of methotrexate and improve bioavailability, permeability, and explore other delivery routes, a proline prodrug of methotrexate was synthesized and preformulation stability studies were conducted under accelerated conditions to assess compound liability and possible conversion to the parent drug. Forced degradation studies showed that the prodrug will degrade in the presence of water, acid, Read More

Hepatitis C virus (HCV) NS5B polymerase is the key replicating protein of the virus and thus an attractive target for drug development. Here we report on the synthesis and biological evaluation of a new series of benzimidazole derivatives as HCV NS5B inhibitors. This yielded compound 6b and 6d bearing 2-(2-benzyloxy)phenyl and 2-(4- methylbenzyloxy)phenyl moieties, respectively, as promising leads. Binding mode of co Read More

With a view to the rational design of a selected series of 35 imidazopyridazine derivatives, 2D and 3D QSAR models have been developed for the prediction of antimalarial activity. The statistically best 2D QSAR model having r2 = 0.9242 and q2 = 0.8691 with pred_r2 = 0.9206 was developed by SW-MLR and best 3D QSAR model having q2 = 0.8607 with pred_r2 = 0.8332 was developed by k-nearest neighbor molecular field an Read More

A quantitative structure-activity relationship (QSAR) study has been made on a novel series of pyrrole derivatives acting as lymphocyte-specific kinase (Lck) inhibitors. The Lck inhibition activity of compounds is found to be significantly correlated with their molar volume (MV) and surface tension (ST) and the hydrophobic constant of one of their substituents. Both the molar properties MV and ST of the compounds are foun Read More

This paper presents results of QSAR (Quantitative Structure Activity Relationship) studies realized with the PRECLAV (Property Evaluation by Class Variables) software. The database contains 66 derivatives of aromatic benzene sulfonamides incorporating 1, 3, 5-triazine moieties, fluorophenyl sulfamates, S-substituted-2-mercaptobenzenesulfonamide and diazenylbenzenesulfonamides with clinically used CA inhibitors. For each Read More

Group based Quantitative Structure Activity Relationship (GQSAR) was developed for thirty (4-keto-phenoxy) methyl biphenyl-4-sulfonamides which exhibit aggrecanase-1 enzyme inhibitory activity. This enzyme is involved in osteoarthritis. The data is divided into training and test sets, where the latter is used for validating the model. Substitution in the R1 position plays a major role when compared to substitution in R2 position. Th Read More

The synthesis and biological evaluation of hybrid opioids consisting of Naloxone or Naltrexone and a partial opioid peptide are described. These compounds were synthesized in a homogeneous solution as well as in solid phase. A hydrazone linkage was employed to connect the alkaloids to the tetrapeptides. In synthesizing the peptides some non-traditional methods, which provided excellent results, were explored. The solid Read More

In this paper the authors investigated a synergistic antimycotic effect between four antifungal drugs Amphotericin B, Fluconazole, Tioconazole, and Flucytosine individually combined with Anidulafungin compound. This latter is considered a drug of choice in the treatment of fungal infections; it has good activity both in vitro and in vivo against yeasts and moulds, as Candida and Aspergillus. The goal of this study was to evaluate t Read More

Dopamine (DA) agonists, bearing catechol or phenol rings, are endowed with low oral bioavailability and short effect duration. In this report, the synthesis of novel differently substituted 4-(3-pyridyl)-1,2,3,4-tetrahydroisoquinolines and (1,2,3,4-tetrahydroisoquinolin-4-yl)phenylmethanols as potential non phenolic and non catecholic DA receptor ligands is reported. The new compounds, evaluated by binding tests on cerebral s Read More

Acylhydrazide Schiff bases 1-27 were evaluated for their in vitro DPPH radical and superoxide anion scavenging activity. They showed a varying degree of DPPH radical scavenging activity with IC50 values between 31.25 - 473.59 µM. Compounds 8, 2, and 10 have IC50 values 31.25 ± 1.32, 34.40 ± 0.66, and 37.24 ± 0.4 µM, respectively. Standard npropylgallate showed an IC50 value 30.12 ± 0.27 µM. Acylhydrazides 1-27 ex Read More

Multidrug resistance in cancer is a major cause of failure in cancer chemotherapy. In search of new compounds with strong reversal activity and simple molecular structure, we have synthesized a series of compounds in which different substituents were linked to the 2-position of the 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)- tetrahydroisoquinoline system. Compounds were analyzed for their cytotoxicity by MTT in K562 cell Read More

A QSAR study was performed on ninety eight substituted biphenyl analogues of 2-nitroimidazo-[2, 1-b] [1, 3]- oxazines as antitubercular agents to explore the importance of topological, thermodynamic, spatial and physicochemical properties of the molecules towards the antitubercular activity. Genetic function approximation (GFA) was used as the chemometric tool for the study. The study shows that ortho and meta linked attac Read More

Folic acid receptors (FR) are usually over expressed in many cancer cells and are considered as potential targeted therapy agent. Generation of five polyamido amine (PAMAM) dendrimer folic acid conjugate was synthesised and radiolabelled with 188Re, furthermore the in vitro/in vivo stability was evaluated accordingly. The labelling yield of the conjugate G5-FA-DTPA-188Re was 67.1 % and its radiochemical purity exce Read More

The development of new antimicrobial agents for the treatment of infectious diseases remains challenging due to the increasing impact of antibiotic resistance. Since salicylanilides and esters of pyrazine-2-carboxylic acid have been described as potential antimicrobials, we have designed and synthesized a series of 2-(phenylcarbamoyl)phenyl pyrazine-2-carboxylates. These were evaluated in vitro for the activity Read More

Fifteen derivatives of 8-oxocoptisine were prepared based on that 8-oxocoptisine showed potent reversing effect against human cancer cells charactering multidrug resistance (MDR). The derivatives were evaluated for their growth inhibition and effects on reversing P-gp-mediated MDR against MCF-7/AMD cells. 12, 13-dinitro-8-oxocoptisine (6c), the most potential candidate with weak growth inhibition, significantly increa Read More

The role of vasopressin (AVP) in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is elevated in heart failure and some forms of hypertension. Also, AVP has vasoconstrictor, mitogenic, hyperplasic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Furthermore, cholesterol blood levels are also associated w Read More

Poor bioavailability of topically instilled drug is the major concern in the field of ocular drug delivery. Efflux transporters, static and dynamic ocular barriers often possess rate limiting factors for ocular drug therapy. Different formulation strategies like suspension, ointment, gels, nanoparticles, implants, dendrimers and liposomes have been employed in order to improve drug permeation and retention by evading rate limiting fa Read More