Pharmaceutical Chemistry Journal最新文献

Analytical results for different dosage forms of ophthalmic drugs for the quality indicator “Particular contamination – subvisible particles” are presented. The possible analytical methods and regulatory requirements applicable to the quality of ophthalmic drugs for this parameter are discussed. Analytical results for subvisible particulate matter in ophthalmic dosage forms (40 samples) are presented. The need to introduce modern standardization of subvisible particulate matter in eye drops that is harmonized with leading pharmacopoeias is demonstrated.

The diterpenoid isosteviol is one of the stevia derivatives that have reported various activities. In mice inhaling isosteviol, OVA- and ACh-induced bronchial asthma showed a dose-dependent improvement of a decline in the expression of inflammatory cytokines and the infiltration of basophils. Compared with inhalation of budesonide 0.6 mg/kg, sensitized mice inhaling 1.0 mg/kg dosage of isosteviol performed a higher tolerate against the ACh stimulation. In behavior tests, the 1.0 mg/kg isosteviol nebulization reached almost 80% of the level of budesonide with regard to the ameliorative effects on depression-like behavior and improvement in sport ability. In addition, lung and systemic inflammation were markedly prevented by isosteviol with a dosage of more than 0.6 mg/kg, which exhibited limited expression of IL-1β and TNF-α, less infiltration of basophils in lung tissues, and a low level of systemic immunocytes, which showed in hematoxylin and eosin staining, RT-PCR, and ELISA results. On the other hand, none of the abnormal pathology was found in both peripheral and central organs of all the administration groups. Generally, this study implicated that the mechanism could involve effects of isosteviol inhalation on the suppression of IL-1β and TNF-α to restrict a systemic upsurge of immunocytes and infiltration into the lung that prevents the occurrence of depression-like behavior and hypokinesia.

The steroid hormone 5-androstenediol (5-AED) has been advanced as a possible countermeasure for protection from ionizing radiation. It is highly effective both before and after exposure to ionizing radiation and is safe and well-tolerated. 5-AED prevents radiation-induced suppression of hematopoiesis by increasing the survival of bone-marrow cell progenitors and the numbers of circulating neutrophils and platelets. The radioprotective effectiveness of 5-AED is based on stimulation of G-CSF synthesis through NF-кB pathway activation, inhibition of pyroptosis and apoptosis, repair of radiation-induced DNAdamage, and increased expression of inducible NO-synthase genes. Development of new synthetic 5-AED derivatives helps to enhance its bioavailability and makes 5-AED a prospective molecule for creating novel safe and effective radioprotective drugs.

Despite the important role that urease plays in the global nitrogen cycle, inhibition of its activity is demanded owing to the development of diseases such as stomach ulcers and some cancers. In the search for a potent urease inhibitor, imidazoacridine and pyrazoloacridine derivatives were synthesized and evaluated for their urease inhibitory potential. The desired compounds were obtained in two steps at high yields in basic media. Title compounds exhibited a variable degree of inhibitory interaction potential having IC₅₀ values ranging between 14.83 ± 0.03 and 22.21 ± 0.6 μM compared with standard thiourea. To understand the binding interaction of most active analogs with ab active site of urease enzyme, molecular modeling of the complexes (ligand–enzyme) was also performed.

Many heterocyclic triazole rings and compounds containing triazole rings exhibit diverse biological activities. Heterocyclic derivatives of this class possess significant value for the discovery and development of new anticonvulsant medications as a result of successful synthesis of various triazole derivatives that hit the market for pharmaceuticals as CNS stimulants. The two isomers of triazole containing derivatives are 1,2,3-trizoles and 1,2,4-triazoles. From these two, 1, 2,4-triazole containing drugs exhibit a variety of pharmacological effects, including antimycobacterial, antitubercular, anticancer, anticonvulsant and herbicidal properties. Consequently, triazole-containing molecules function as potentially effective drug and may be useful for the design and development of new triazole derivatives that could be more efficacious and less toxic. This review summarizes data on various triazole derivatives and their significance.

Results from studies of the antidiabetic and antihyperglycemic activity of a low-molecular-weight NGF mimetic, compound GR-2 [bis-(N-monosuccinyl-L-glutamyl-L-lysine)hexamethylenediamide], on a streptozotocin-induced diabetes model in Wistar rats are presented. GK-2 administered perorally at a dose of 5 mg/kg for 28 d significantly reduced the glycemia level in diabetic rats and increased the overall plasma antioxidant capacity. The glycemia level and plasma antioxidant capacity were in an inverse exponential relationship and were closely correlated to each other (correlation coefficient 0.899).

The synthesis and in silico prediction of the molecular-targeted anti-EGFR inhibitory activity of a novel dihydroacridinone derivative are reported. 9-Aminium-3,3-dimethyl-3,4-dihydroacridin-1(2H)-one L-2-hydroxybutanedioate (LHT-17-19) was obtained 99.8% pure by mixing and heating equimolar amounts of 9-amino-3,3-dimethyl-3,4-dihydroacridin-1(2H)-one and L-2-hydroxybutanedioic acid in 50% EtOH. Virtual molecular screening of the spectrum of effects of the compound revealed inhibitory properties against several intracellular targets, i.e., carcinogenesis drivers, among which the EGFR kinase domain had the highest probability. Docking of LHT-17-19 base to the EGFR kinase domain formed a molecular complex with a high affinity and bonding energy. The results suggested that LHT-17-19 had high antitumor activity against malignant neoplasms expressing EGFR.

Comenic (5-hydroxy-4-oxo-4H-pyran-2-carboxylic) acid is regarded as a new analgesic agent. Comenic acid (CA) was studied in acute pain models using Wistar rats in the tail-flick and hot-plate tests. CA was administered in a single intramuscular injection 30 min before the tests. The reference drug (INN diclofenac) was administered at a dose of 6.6 mg/kg; the test drug (CA solution), at doses of 20, 40, and 60 mg/kg. Tests were performed 15 min and immediately before CA administration and 30, 45, and 60 min after administration. The maximum possible effect (MPE) was calculated for each test at the end of the studies. No statistically significant differences were found between experimental groups in the tail-flick test. The MPE in the hot-plate test for the test and reference drug groups was significantly higher than that in the control group at all time points (30, 45, and 60 min after administration of the drugs). CA was found to have a lesser effect on the formation of a spinal reflex (tail-flick test) but was rather effective in tests involving supraspinal structures (hot-plate test). No toxic manifestations (according to clinical observation and animal body weight) and dose dependence were identified.

To improve and develop our monotherapeutic approach for Helicobacter pylori infection, some Schiff base compounds containing eugenol and guaiacol were synthesized and their antioxidant capacities, urease enzyme inhibition, and Anti-Helicobacter pylori effect were investigated and compared with azo analogs in the literature. All Schiff base compounds have been found to have both stronger urease enzyme inhibitory and more effective Anti-Helicobacter pylori properties than its azo analogs. In particular, the antimicrobial effect of Schiff bases containing eugenol increased dramatically when compared to their azo analogs.

A modified method for the synthesis of a promising non-narcotic analgesic agent of the hexaazaisowurtzitane class with pronounced anti-inflammatory activity is described. Methods for reducing the cost of the target substance are considered. The physicochemical characteristics are described. The efficacy and safety of the synthesized agent are shown in several animal models.