Медицинская химия

A novel series of 1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one derivatives were synthesized. The synthesis started with the important building block 3, which was prepared via coupling of from 2-(bi's (methylthio) methylene) malononitrile 1 with 4-amino-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one 2. The 5-aminopyrazole derivatives 4-8 were prepared from the cyclocondensationof 3 with the appropriate sulfonohydrazides and pyridine- 4-carbohydrazide respectively. Cyclocondensation of 1 or 9 with pyridine-4-carbohydrazide and 4-methylbenzene sulfonohydrazide corresponding pyrazole derivatives 10, 11, 12 and 13. Condensation 2 and 1-isothiocyanato-4- methylbenzene 14 yielded 15 which was refluxed with malonic acid to yielded1-(1,5-dimethyl-3-oxo-2-phenyl-2,3- dihydro-1H-pyrazol-4-yl)-2-thioxo-3-(2methylphenyl) dihydropyrimidine-4,6(1H,5H)-dione (16). All tested compounds showed analgesic and anti-inflammatory activities in comparison to the reference standard drugs tramadol, acetyl salicylic acid and indomethacin. Maximum protection against the thermal stimulus was observed at 90 min following the administration of the compound (5) (105.8%), which was statistically significant comparable to the reference drug tramadol (148.7%). Compounds (5, 6, 11 and 13) revealed their maximal analgesic effect after 60 min (68.5%, 77.5%, 84.6% and 89.7%, respectively), then their effect started to decrease. In addition, derivatives 10, 12 and 16 showed anti-inflammatoryactivity after 4 hours, which was greater than that of the reference drug indomethacin and reached the maximum effect at the 2nd h. Additionally, a molecular docking study was performed against the COX enzyme using the Molsfot ICM 3.8 software.

IL-1β is an important cytokineinvolved in several immune responses. IL-1β exerts its effect by binding with its receptorcalled IL-1R1 and leading to a series of intra-cellular signalling. The over-expression of IL-1β leads to immunological complications including arthritis and auto-immune disorders. Currently there are several drugs in the market to cure the inflammation either by inhibiting the production of IL-1β or affecting its signal cascade. The hindrance in the interaction between IL-1β interaction and its receptor can stop its function hence hope to cure inflammatory diseases. This study presents a docking analysis of five commercially available drugs at the IL-1β/IL-1R1 protein interface. This study would give an insight for designing the drugs, capable to block the direct interaction of IL-1β with its receptor ultimately leading to some more consistent cure for inflammatory diseases.

Radiation dermatitis occurs in up to 95 percent of patients receiving radiotherapy. The aim of this study was to evaluate whether topical application of a new Benzene-Poly-Carboxylic Acid and Molybdenum Complex (BP-C2) prophylactically could protect mice skin from irradiation-induced dermatitis or treat irradiation-induced skin dermatitis, when it already has occurred. The right posterior leg of male BALB/cfC3H mice was exposed to radiation dose of 30 Gy. For prevention studies, animals were treated with BP-C2 just prior to irradiation and three times a week for 5 weeks post-radiation. For treatment studies, animals were treated with PB-C2 three times a week for five weeks when skin injury was appeared following irradiation exposure. Animals were sacrificed and skin damage was assessed using a non-linear semi-quantitative scale, as well as histological studies. Acute skin dermatitis was observed in all control animals (n=8) following 30 Gy irradiation in form of edema and ulceration grade 4. No signs of skin dermatitis were observed in the irradiated area of animals (n=8) treated with BP-C2 prior to irradiation exposure. Moreover, treatment of injured animals with BP-C2 three times a week resulted in recovery of the skin and no erythema or ulceration was hereafter observed. BP-C2 represents a potentially promising agent for prevention and treatment of irradiation-induced skin dermatitis.

Many substances of natural origin are contained in pharmaceutical and cosmetic formulations, but lately extra virgin olive oil (EVOO) or EVOO-derived compounds like tyrosol, hydroxytyrosol or oleuropein, thanks to their renowned and long-established outstanding therapeutic and health giving virtues, have made them some of the most interesting products in this field. Nowadays many hydroxytyrosol-based topical formulations are commercialized and over time several analytical methods have been developed. However, new cosmetic formulations containing an olive extract tritated in hydroxytyrosol conveyed in EVOO have recently appeared on the market creating the need to develop and validate a new method that allows the active compound to be extracted and analyzed precluding any interference due to the presence of other compounds naturally present in the EVOO as well as from the co-formulant agents employed, and this has been the goal of our study.
Analytical determination was performed by RP-HPLC coupled with DAD detection. Various chromatographic parameters, namely column stationary phase, mobile phase, pH and solvent composition, oven temperature and different clean-up variables were studied. The best chromatographic separation was obtained under the following conditions: a reverse phase C18 column maintained at 25°C with a gradient elution program using acetic acid 0.2% and methanol as mobile phase pumped at 1.5 mL min−1. Detection wavelength was set at 280 nm and the total run time required was 15 min. The high degree of accuracy (98.8%-100.1%) and precision (1.44%-1.68%) achieved using the evaluated method along with the low limits of detection and quantification (2.49 ppm and 3.97 ppm respectively) and the broad linear range observed allowed the target analyte to be satisfactorily determined in new semi-solid formulation containing hydroxytyrosol conveyed in EVOO while avoiding any matrix effect.