Journal of Reports in Pharmaceutical Sciences
Volume:1 Issue: 2, Jul-Dec 2012

Cancer is a group of diseases characterized by uncontrolled proliferation of abnormal cells. Because of the severe side effects and resistance to the traditional chemotherapeutic agents, the necessity for discovery of new anticancer drugs is a crucial topic. In the present study we synthesized new derivatives of 2-(4-Fluorophenyl)-N-halophenylacetamide and assessed their cytotoxicity against four cancerous cell lines consist of PC3(prostate cancer), Hela(cervical cancer), ACHN(Renal cell carcinoma) and MCF-7(Breast cancer). All compounds demonstrated better cytotoxicity activity toward PC3 cell line. Compound 2b showed the best cytotoxic effect in this series. Replacement of butyl chain with phenyl ring led to the increasing of the cytotoxic effects.

For prolonging the time that drug remains in stomach, new methods used as floating drug delivery systems, that available in various forms such as floating tablets. These systems enhance drug absorption and decrease plasma concentration fluctuations. Iron deficiency and its inadequate absorption in diet are of community health problems. For prolonging the time that drug remains in stomach, new methods used as floating drug delivery systems, that available in various forms such as floating tablets. These systems enhance drug absorption and decrease plasma concentration fluctuations. Iron deficiency and its inadequate absorption in diet are of community health problems. Common forms of iron available in the market have little bioavailability and due to greater excretion of drugs from the gastrointestinal tract has many complications such as constipation. Using floating systems to enhance drug absorption can reduce the dose required and drug side effects. In this study, preparation of floating tablets of ferrous sulfate plus ascorbic acid is considered since it has proven that vitamin C enhances iron absorption. Tablets were prepared with swollen polymers like HPMC K4M and carbopol934 by direct compression method. Sodium bicarbonate and citric acid was used to create the CO2 then drug properties such as buoyancy, release percentage and physical properties were tested on that. Tablet formulation No. 10, started to float in 27 seconds and floating state lasts 18 hours in environments like stomach. According to the great drug release and long floating state (12 h), tablet formulation 10 is recommended as a drug supplement to prevent anemia.

The Leishmaniasis is a zoonotic disease that remains a severe public health problem and its burden is increasing. By now there is no anti-leishmaniasis vaccine and as other tripanosomial disease, is treated by limited drugs. First line drug includes pentavalent Antimony such as sodium stibogluconat and meglumine antimoniate that use of these drugs is limited due to side effects, long term treatment, high cost and incidence of drug resistance. It is clear that developing new, effective, cheap and safe drug is necessary for treating Leishmaniasis. In this study new four derivatives of 1-(5-halo-2-thienyl)-2-[5-(5-nitroheteroaryl)]-1,3,4-thiadiazol-2-ylthio)ethanone were synthesized and target compounds were evaluated against the promastigote form of Leishmania major using MTT assay in comparison with control drug (Fluconazole). Concentrations (5-150 µg/mL) of synthesized compounds and control drug were prepared and IC50 for each compound was measured. IC50 for 8a-d was 114.98 µM (44.59±8.15 µg/mL), 118.05 µM (51.25±9.08 µg/mL), 130.7 µM (52.78±12.97 µg/mL), and 252.7 µM (113.3±5.92 µg/mL) respectively that was less than of fluconazole 980 µM (300 µg/mL). The results of this study showed that four synthesized compounds had a significant effect on Leishmania major and have a stronger effect than control drug. It seems that these compounds can be used as an alternative in future.

In a wide search program towards new and efficient antimicrobial agents, a series of 4-substituted-1,2,4-triazolidine-3,5-dione derivatives namely urazoles holding an alkyl moiety at position 4 have been synthesized and tested for their in vitro antibacterial and antifungal activities. The structures of these compounds have been investigated by spectral data. The synthesized compounds were tested in vitro against two Gram-positive, six Gram-negative bacteria, and the yeast Candida albicans (clinical isolated) in comparison with several control drugs. The antioxidant activity of the tested compounds was also assessed by 2 tests highly documented in the literature: capability to prevent lipid peroxidation, and direct scavenging effect on a stable free radical, 1,l-diphenyl-2-picryl-hydrazide (DPPH).

Interaction of drugs with serum albumin, the most abundant protein in plasma, has a great significance in pharmaceutical sciences. It can affect the biological activity, toxicity, and pharmacokinetics of drugs and design of dosages. Determination of the impact of chemical modifications of albumin and its structural changes upon interaction with drugs are very important when drugs bind with albumin to a significant degree. Hypochlorite is naturally produced by activated phagocytes in vivo at inflammatory conditions. In current study, the effects of hypochlorite-mediated oxidation on the albumin stability, surface hydrophobicity and its interaction with furosemide were investigated using intrinsic and extrinsic fluorescence techniques. Bovine serum albumin (BSA) was chemically modified with sodium hypochlorite under nondenaturing conditions. The Job’s plot indicated that the drug binds to the unmodified and modified BSAs with a 1:1 stoichiometry. Fluorescence quenching data showed that the albumin affinity for the drug as well as its surface hydrophobicity increases under the effect of protein oxidation. Measurement of conformational stability indicated that oxidized BSA is less stable compared to the unmodified protein. Thermodynamic analyses of the binding process showed that the major forces involved in the interaction of furosemide to the unmodified and oxidized BSA are same (hydrophobic). Increment of protein surface hydrophobicity (PSH) as well as the decrement of protein stability may reminiscent of higher protein structural flexibility upon oxidation which may affect the drug binding site.

9-nitrocamptothecin (9-NC) is a semisynthetic and a low soluble analogue of camptothecin alkaloids that target nuclear enzyme topoisomerase I. The unsTable lactone form of 9-NC in biological fluids requires for its cytotoxic activity. To improve aqueous solubility and stability in biological media, 9-NC was loaded in polymeric nanoparticles. In this paper, we studied the effect of PEG percent (0, 5, 10, 15) in PLGA-PEG copolymer on physicochemical properties of nanocarriers. To acquire an optimum formulation, a Generalized Regression Neural Networks (GRNN) and a Multi-Layer Perceptron (MLP) as potent statistical methods were employed. The drug loaded parameters were the input vectors of the GRNN and included the amount of polymer and emulsifier, volume of external and internal phases. The nanoparticles drug loading constitutes the output vector of each network. In this way, GRNN and MLP are trained to investigate the functional influence of input variables on the output response.PLGA-PEG nanoparticles were prepared by nanopercipitation method. Zeta sizer, DSC, SEM and frantz diffusion cell were used to measure physicochemical properties of optimized formulations.The physicochemical properties of 9-NC nanoparticles influenced by PEG percent in PLGA-PEG copolymer. Drug loading increased which can be attributed to the hydrophobic nature of drug and amphiphilic nature of copolymer. The size of nanoparticle decreased by increasing the PEG percent in copolymer which can be attributed to emulsifing nature of PEG percent. Release rate decreased by increasing the percent of PEG in PLGA-PEG nanoparticles but in vitro stability increased. DSC thermograms and FT-IR results showed that 9-NC was encapsulated in PLGA-PEG nanoparticles in its amorphous form.According to artificial neural network (ANN) data, we found that PLGA-PEG (15%) had best physicochemical characteristic compare to other copolymer. The optimum formulation showed that these nanoparticles could be hopeful and potential carriers for delivery of unsTable and low soluble drugs especially anticancer agents.

Thirty nine novel 1,2,3,4-tetrahydropyrimidinone (thione)s were subjected to conformational studies. Density functional theory at B3LYP/6-31 G* was performed as the computational method of high accuracy. Important dihedral angles and bond lengths were investigated and the values obtained were explainable. Results of this work confirm a twisted boat tetrahydropyrimidine ring conformation with an axial C4 substituent for most of the compounds. This substituent was oriented toward the C5 atom. The carbonyl group located on the C5 substituent and the C5=C6 bond had both s-cis and s-trans conformation in the studied molecules.

Vascular adhesion protein-1 (VAP-1) is an endothelial cell surface-expressed oxidase involved in leukocyte traffic. The adhesive function, and therefore leukocyte infiltration to different tissues, can be blocked by anti-VAP-1 antibodies as well as small molecule VAP-1 inhibitors. Several papers have been published on the effect of VAP-1 blockade on both leukocyte accumulation into tumors and neoangiogenesis. Additionally, myeloid derived suppressor cells (MDSCs) have been identified as immunosuppressive cells associated with tumor expansion. Moreover, some of them (such as CD11b+ myeloid cells) appear to be intrinsically suppressive and may have a key role in maintaining immune homeostasis and protection from autoimmunity. Since VAP-1 supports leukocyte emigration (including MDSCs) to normal tissues and sites of inflammation like tumor tissue, its inhibition has been suggested as potential cancer immunotherapy intervention. Moreover, since these types of suppressive cells use VAP-1 mediated strategy for their adhesion and infiltration, it is hypothesized that VAP-1 inhibition may lead to partial loss of suppressive function on immune system and therefore induce the development of autoimmune diseases like relapsing-remitting (experimental) autoimmune encephalomyelitis.