Pharmaceutical Chemistry Journal最新文献

The structure of enterosgel before and after freezing (samples I and II, respectively) was comparatively analyzed by gravimetric analysis and NMR methods [PMR, ¹³C NMR, diffusion-ordered NMR spectroscopy (DOSY)] to understand the reason for the negative effect of freezing on the adsorption capacity of enterosgel. The methylsiloxane moieties in samples I and II were shown to be magnetically equivalent by PMR and ¹³C NMR methods. The molecular masses of samples I and II were estimated by the DOSY method and corresponded to the cyclic dimer of methylsilicic acid (MM 152 Da) for sample I and the linear dimer of methylsilicic acid (MM 170 Da) for sample II. It was hypothesized that the conformationally rigid cyclic dimer structure was destroyed upon freezing of enterosgel due to rupture of a siloxane bond. The adsorption capacity of enterosgel deteriorated because of the structure disruption and hydrophobicity change. Thermogravimetric analysis revealed that water did not participate in hydrogen bonding with enterosgel.

Hydrogel films with a polymer base of corn starch and poly(vinyl alcohol) (50:50 wt%), citric acid as a crosslinking agent, and glycerin as a plasticizer were synthesized. Their physical and mechanical characteristics corresponded to the performance level of commercial wound dressings of the same type. The degree of swelling increased by ~30%, whereas the elastic modulus and water-vapor permeability decreased by ~60% when ethonium was introduced into the polymer matrix (from 1 to 5 wt% of the polymer weight). Drug release from the polymer matrix occurred within 90-105 min at drug contents of 2.5-5 wt%. The developed films inhibited the growth of the microorganisms E. coli and P. aeruginosa.

A series of 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6-aryl-2,3,4,5-tetrahydro-pyridazin-3-one (4a-e) was synthesized and evaluated for its in vitro antimycobacterial activity. All the synthesized compounds were structurally confirmed by using physicochemical and spectral analysis such as melting point, R_f value, elemental analysis, IR, NMR and mass spectra. In vitro antimycobacterial activity was screened by the microplate Alamar Blue Assay (MABA) method against Mycobacterium tuberculosis H37Rv strain. Derivatives with 4-ethyl phenyl substitution (4b) and chloro phenyl substitution (4e) at the p-position of pyridazinone nuclei showed good antimycobacterial activity with a MIC value of 6.25 μg/ml compared to other aryl substitutions such as 4-methoxy phenyl (4a), 4-methyl phenyl (4c) with a MIC value of 25 and 12.5 μg/ml. The results of in vitro antimycobacterial activity revealed that the synthesized compounds have potential antimycobacterial action and can be further optimized and developed as lead compounds.

Corneal epithelial injury is a high-incidence corneal disease. The purpose of this research is to determine how basic fibroblast growth factors affect bFGF and Carbomer (CAR) long-acting hydrogel eye drops regarding the repair of corneal epithelial injury. Liposome hydrogel eye drops containing both bFGF and CAR were prepared by a thin film hydration method (bFGF-CAR-HED). Particle size, potential and transmission electron microscopy were used to characterize the performance. UV was used to calculate the encapsulation rate, drug loading, and in vitro release. The antioxidant capacity was detected by ABTS and FRAP. Safety was evaluated by cell assay. After parallel mechanical corneal epithelium injury in normal mice, the repair of corneal epithelium injury, sensitivity repair and the expression of inflammatory factors in the cornea were detected. bFGF-CAR-HED is a multilayer liposome with good stability with a particle size of 308.4 ± 7.25 nm, and a potential of 36.3 ± 6.27 mV. The encapsulation rate of bFGF in bFGF-CAR-HED was 92.01 ± 1.05%, the encapsulation rate of CAR was 91.94 ± 0.34%, the drug load of bFGF was 18.82 ± 0.35%, and the drug load of CAR was 19.97 ± 0.39%, which showed sustained release function, low cytotoxicity and good antioxidant capacity. Long-acting hydrogel eye drops can strengthen drug application performance and extend the time of drug action, effectively improving bFGF, eye absorbency and the function of CAR, effectively promoting corneal epithelium damage repair and restoring corneal sensitivity, thereby providing better strategies for promoting corneal epithelium damage repair.

A method for quantitative determination of myricitrin in common myrtle (Myrtus communis L.) leaves using high-performance liquid chromatograph (HPLC) was developed. The content of the dominant flavonoid myricitrin (myricetin 3-O-α-L-rhamnopyranoside) in common myrtle leaves varied from 0.98 ± 0.02% to 1.51 ± 0.07%. The error of a single determination and the average error of the myricitrin content determination in common myrtle leaves were ±15.81% and ±4.77%, respectively, with confidence probability 95%.

Two types of known and new derivatives of substituted β-cycloketols were synthesized; characterized using IR, PMR, and ¹³C NMR spectroscopy; and tested for neurotropic activity. Bioscreening of the compounds was performed. A study of the neurotropic properties of the synthesized new β-cycloketol derivatives revealed that some of them exhibited a pronounced anticonvulsant effect as antagonism of corazol. The compounds were superior in anticonvulsant activity to the well-known drug ethosuximide but inferior to diazepam. Like ethosuximide, the studied compounds did not exhibit central muscle relaxant activity at anticonvulsant doses, unlike diazepam. However, they exhibited psychotropic effects, e.g., pronounced anxiolytic, antidepressant, and activating behavior. The results showed that further searching for neurotropic properties in new polyfunctional cycloketol derivatives was advisable.

The heterocyclic nucleus has a wide range of biological activities with the benzimidazole nucleus having diverse biological activities such as antifungal, antihistaminic, anti-convulsant, anti-inflammatory, analgesic, antiviral agents, etc. From an in-depth literature review, we have complied here a green synthesis of benzimidazole derivatives that are antifungal agents. This review is intended to be of assistance to the scientific community working in the area of heterocyclic nuclei.

A new group of unsymmetrical ALM-802 analogs, N¹-benzyl-N²-{2-[(2,3,4-trimethoxybenzyl)amino]-ethyl}ethane-1,2-diamines of general formula 1, in which one of the aromatic groups was changed, was studied. The anti-ischemic and antiarrhythmic activities of the new compounds were studied. Their ADME characteristics were analyzed. The 2,3,4-trimethoxyphenyl group used as one of the aromatic pharmacophores was shown to play a key role in the activity of compounds of this type. The presence of a second aromatic group was also important since its removal led to the disappearance of cardiotropic activity. However, its structure had significantly less impact on the activity of the corresponding compounds because a rather wide variation of substituents in this group did not change the activity in most arrhythmia and ischemia models.

Fullerene C₆₀ exhibits potent antioxidant anti-inflammatory activities as well as anticancer activities. In this study using 60 Wistar albino female rats (n = 60, 8 weeks old), they rats were divided into 4 groups, including 15 rats each. The groups were arranged as follows: (i) Control Group: Group fed with standard diet; (ii) C₆₀ Group: C₆₀ (1.7 mg/kg bw, oral gavage); (iii) DMBA (7,12-dimethylbenz[a]anthracene) Group: DMBA (45 mg/kg bw, oral gavage); (iv) C₆₀ and DMBA Group: C₆₀ (1.7 mg/kg bw, oral gavage) and DMBA (45 mg/kg bw, oral gavage) group. DMBA increased the malondialdehyde levels in muscle tissue, while decreasing GSH and CAT levels; however, treatment with fullerene C₆₀ reversed these effects. In addition, the oral administration of fullerene C₆₀ increased caspase-3 and Nrf-2 protein expression and significantly decreased Bcl-2, NF-κB, TNF-α, COX-2 and p38α (MAPK) protein expression in C_{60 +} DMBA compared to the DMBA group. Moreover, histopathological imaging revealed that the oral administration of fullerene C₆₀ decreases inflammatory cells, edema formation, and hydropic degeneration in the muscles. Taken together, the results of the present study indicated that fullerene C₆₀ nanoparticle provides effective protection by preventing muscle tissue damage.

The extract obtained from the aerial part of Datura stramonium by treatment with EtOH (90%) was fractionated with various organic solvents. Use of extraction naphtha produced 0.28% (in percentage of the raw material mass) of the extracted substances; CHCl₃, 2.24%; EtOAc, 1.19%; and n-BuOH, 12.43%. Six withanolides such as daturalactone (I), (22R)-7b,27-hydroxy-1-oxowitha-2,5,24-trienolide (II), daturataturin A (III), withastramonolide (IV), (22R)-27-hydroxy-7b-methoxy-1-oxovita-3,5,24-trienolide (V), and daturametelin H (VI) were isolated from the aerial parts of D. stramonium collected in the Fergana Region of Uzbekistan. Their structures were elucidated on the basis of vast data of IR, UV, and NMR spectroscopic studies. The presence of compounds II, III, and V in the aerial parts of D. stramonium growing in Uzbekistan was proven, while compound VI was isolated for the first time from aerial parts of D. stramonium. The cytotoxicity of chemically pure daturametelin H was studied on cancer cell lines such as cervical epithelial carcinoma HeLa, mammary adenocarcinoma HBL-100 (ATCC NTV 124), adenocarcinoma of the larynx HEp-2 (ATCC:CCL-23), and T-lymphoblastic leukemia CCRF-CEM (ATCC:CCL-19). Daturametelin H was found to exhibit pronounced cytotoxicity at a concentration of 100 mM only against T-lymphoblastic leukemia cells in vitro.