Open Medicinal Chemistry Journal最新文献

Biopharmaceuticals are often produced by recombinant E. coli or mammalian cell lines. This is usually achieved by the introduction of a gene or cDNA coding for the protein of interest into a well-characterized strain of producer cells. Naturally, each recombinant production system has its own unique advantages and disadvantages. This paper examines the current practices, developments, and future trends in the production of biopharmaceuticals. Platform technologies for rapid screening and analyses of biosystems are reviewed. Strategies to improve productivity via metabolic and integrated engineering are also highlighted.

In this paper we show that controlling adhesion in highly flexible nanovectors can help in smartly delivering the drug. The high flexibility of the nanovector is used to smartly deliver the drug only at the target site by the new concept of "adhesion induced nanovector implosion"; a liquid drop analogy is developed for the calculations.

The article discusses the application of vibrational spectroscopy techniques for in vivo identification and characterization of glucose biomolecules monitored in the skin of healthy, prediabetes and diabetes subjects; for molecular characterization of water and proteins in in vivo monitored patch tested inflamed skin of the patients with contact dermatitis; for description of nucleic acids and proteins at the molecular level with progression to malignancy in skin cancerous lesions. The results of the studies show new possibilities to assess activity levels of glucose metabolism in the skin tissue of healthy, prediabetes and diabetes subjects; activity and severity of inflammation; activity of the processes of carcinogenesis with regard to benign, premalignant and malignant transformation. Based on our findings, we suggest that vibrational spectroscopy might be a rapid screening tool with sufficient sensitivity and specificity to identify and characterize skin biomolecules in described diseases for drug targeting and monitoring by the pharmacological community.

Results from our group showed benzyl salicylate to be a moderate inhibitor of the CD81-LEL-HCV-E2 interaction. To increase the biological activity, heterocyclic substituted benzoic acids were coupled to amino acid esters via microwave assisted DCC-reaction. The prepared compounds were tested for their inhibitory potency by means of a fluorescence labeled antibody assay system using HUH7.5 cells.

Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of cyclobutane-containing alkaloids as an important source of leads for drug discovery.

This project explores molecular models of Survivin Delta-Ex3, H-Ras, and their binding sites, and generates energy optimized 3D coordinates of docked poses and conformations of the XY2 ligand molecule in the active site of Delta-Ex3. The aim is to propose an effective anti-cancer drug that induces apoptosis and inhibits tumor angiogenesis.

Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). We sought to determine INR taking into account only active coagulation factors FII, FVII and FX without inhibition in patient plasmas and calibrator kits.We measured PT using a combined thromboplastin reagent. The calculation was based on a new PT method, which measures active coagulation factors (F II, F VII, FX) and corrects the errors caused by inactive coagulation factors.On this basis, an INR result with and without inhibition for individual patient samples was also calculated and applied to 200 plasma samples obtained from OAT patients. Conspicuous variation in inhibition between the four calibration kits was noted. The kinetics of this inhibition was closest to a noncompetitive pattern.The need of correction for INRs of single patients increases with higher INRs. At the same level of patient INRs the coagulation inhibiton varies markedly.It has been known that different thromboplastin reagents possess variable sensitivities, but this may depend on sensitivity in inactive coagulation factors. PT methods today measure the sum of active coagulation factors and inhibition of inactive coagulation factors. ISI calibrators contain variable amounts of inactive coagulation factors, which renders harmonisation of INR results.Application of the Acf-PT (INR(Acf)) presented in this work develops the PT methodology to measure the true coagulation activity in vivo for patient warfarin therapy without inhibition. INR(Inh) can evidently also be used for the diagnostics and follow-up of certain liver diseases.

Formaldehyde (HCHO) and protoporphyrin, are in connection with redox homeostasis. Data show the importance of HCHO in proliferative as well as in apoptotic processes. Free protoporphyrin can be detected near the Zn-protoporphyrin in cancer and it has pro- and antioxidant forms depending on concentrations. The aim was to determine the amount of HCHO and protoporphyrin concentrations of erythrocytes in colorectal cancer after colectomy and to estimate redox homeostasis. Total 32 adult patients after 5-10 years of colectomy and 9 healthy volunteers were drawn into this study. Tumor markers, redox parameters, HbA1c, HCHO and protoporphyrin concentrations were measured. Erytrocyte HCHO was significantly lower in colectomysed patients, than in controls. Protoporphyrin concentration was low in patients, but in metastasis its concentration was significant. HbA1c correlated significantly with free radicals and decreased the antioxidant status of erythrocytes. HCHO and protoporphyrin concentrations of erythrocytes and the total scavenger capacity are very important indexes in cancer.

Many diabetic patients take several medications to treat diabetes-associated complications and other ailments. The mode of elimination of these drugs and their metabolites are poorly understood. The elimination of deprenyl, a MAO-B inhibitor, used for the treatment of the early stage of Parkinson's disease and senile dementia was investigated using thin layer chromatography.Male Wistar rats (180-200 g) were rendered diabetic by streptozotocin (STZ) treatment (60 mg/kg, i.v.). Rats having at least three times higher plasma glucose level than the normal were considered diabetic. Rats were treated with a single oral dose of 5 mg/kg (14)C-(methyl)-labeled (-)-deprenyl, 98 microCi/mg. Diabetic rats excreted the majority of urinary radioactivity in 8 hours, while control rats did it in 16 hours. The approximate ratio of major metabolites as determined using thin-layer chromatography did not change. In conclusion, diabetic rats excreted radiolabelled-deprenyl more rapidly compared to control animals. Increased elimination of deprenyl should be taken into account in the management of patients suffering from diabetes.

The Flex-Het compound 10a (SHetA2-NSC 721689) {[4-nitrophenylamino][(2,2,4,4-tetramethylthiochroman-6-yl)amino]methane-1-thione]} has shown promise in preclinical testing as an anti-cancer agent without evidence of toxicity, skin irritancy, or teratogenicity. One objective of this study was to synthesize a series of heteroarotinoids structurally related to SHetA2 and to measure the effect of structural alterations on the cytotoxicity activities of the compounds on A2780 ovarian cancer cells. Alterations included comparisons of activity of an NO2 end group versus a CO2Et end group, a thiourea linker versus a urea linker, and a distorted, thiochroman ring unit versus a planar quinoline ring unit. Cytotoxicity assays demonstrated the thiourea linker compounds to be similar in potency to the urea linker counterparts, the NO2 substitutions were slightly more potent than the CO2Et substitutions, and replacement of the thiochroman group with a planar quinoline fused ring system markedly reduced activity. The mechanism of cytotoxicity through apoptosis was confirmed for the compounds. The optimal combination of structural features for enhancing potency consisted of a urea linker, a NO2 substitution, and a flexible thiochroman unit. Extensive H-bonding in the more active urea derivative was confirmed by X-ray and NMR analyses. This is the first example in which the biological activity of flexible, thiochroman units is compared to that of fused aryl units in a heteroarotinoid molecule.