Pharmaceutical Chemistry Journal最新文献

In recent years, there has been growing exploration of organometallic transition metal complexes as promising options for developing anticancer agents that offer the potential of reduced toxicity compared with the commonly utilized cisplatin analogs. In this respect, iridium complexes containing 2-phenylimidazo- [4,5-f][1,10]-phenanthroline derivatives with different substituents were investigated in different cell lines as potential anticancer agents. All the compounds exhibited potent cytotoxic activity against Caco-2, HeLa, A549, and MDA-MB-231 cell lines. EC₅₀ values of compound 1 were found to be 6.44 μM for Caco-2, 24.78 μM for HeLa, 9.14 μM for A549, and 4.45 μM for the MDA-MB-231 cell line. Similarly, EC₅₀ of 3 was found at 15.07, 14.15, 10.33, and 4.48 μM respectively. The EC₅₀ value of 2 was found to be 12.71 μM for Caco-2, 24.31 μM for HeLa, and 7.44 μM for MDA-MB-231 cells. EC₅₀ values of compound 4 were found to be 28.20 μM for Caco-2, 12.79 μM for HeLa, 8.33 μM for A549, and 3.76 μM for the MDA-MB-231 cell line. The results of gene expression and flow-cytometry analysis showed that the compounds caused the induction of apoptosis in all cancer cell lines by changing caspase 3, Bcl-2, and Bax proteins. The obtained results demonstrate that compounds could be introduced as potent agents to prevent the progression of certain types of cancer. However, preclinical and clinical trials will be needed to evaluate these complexes to obtain safe, effective, and optimal therapeutic drugs for cancer patients.

Analytical quality by design-based HPLC procedure has been developed for the estimation of Abrocitinib in bulk and tablets. Design-Expert^®-13 was employed for Response Surface Methodology. ANOVA was applied for responses statistical analysis. Buffer pH, flow rate, % organic composition of mobile phase, column and organic modifier were considered as CMPs. Retention time, number of theoretical plates and tailing factor were considered as CQAs. The CMPs that have a significant impact on CQAs were screened utilizing a 12-run 2⁵ Plackett-Burman design. Following screening investigation, CMPs that have a substantial effect on the CQAs were selected and CMPs of HPLC procedure were optimized employing a 22-run 5³ central-composite design. The optimized procedure suggested by the desirability functions approach utilizing a 55.8:44.2 ratio pH 3.25 ammonium formate buffer and acetonitrile with 1.0 mL/min flow rate as a mobile phase, an Inertsil ODS (150×4.6 mm, 3.5 μm) column as a stationary phase with 5 mins run time resulting in maximum desirability, 1.000. At 3.575 min, Abrocitinib retention time was observed. The optimized procedure was validated and stress studies were executed in accordance to the ICHQ2(R1) and ICHQ1A guidelines respectively. In accordance with the literature, it is evident that this is the initial reported RP HPLC procedure for Abrocitinib estimation.

Thiadiazole and triazole-5-thione derivatives are five membered heterocyclic compounds showing cyclooxygenase inhibition activities. Based on this observation a series of novel aryloxymethyl 1,3,4-thiadiazole and 1,2,4-triazole-5-thione derivatives were synthesized and their biological activities evaluated. The suggested chemical structure of synthesized compounds was confirmed using FT-IR, Mass, ¹H-NMR, and ¹³C-NMR spectrometric methods and elemental analysis. The biological activity or potency of synthesized compounds was evaluated using a COX inhibitor screening assay kit (Cayman Chemical Company), and indomethacin and NS398 as standard compounds. Compounds 2b and 3b showed good inhibitory activity against COX-2 and COX-1 enzymes respectively. The obtained data indicate that compound 2b is more selective to COX-2 and compound 3b is more selective to COX-1 compared with other synthesized compounds. These two compounds show promising selectivity and could be a starting point for future research in this area.

An HPLC-UV method with high sensitivity and good resolution, calculated by the principal component external standard method with correction factors and detailed methodological validation according to ICH guidelines, was developed for the accurate detection of impurities in three different extraction processes of rutin raw materials and their tablets, and the determination of impurity profiles by LC-MS/MS. In this study, nine impurities (>0.1%) were mainly isolated and identified, four of which were process impurities, and the other five were degradation products. The results of the correlation between impurity profiles and production processes showed that the impurity content of rutin tablets correlated positively with the impurity level of the raw materials used, which correlated significantly with the extraction process. The finished rutin under the alkali-dissolution and acid-sedimentation refining method had low purity and the highest impurity content. In contrast, the number of impurities and the total amount of impurities detected in rutin by the secondary recrystallization process with methanol washing were the lowest, and were mainly process impurities. This further indicates that generating degradation impurities could be avoided, and a suitable refining process could effectively reduce impurities. This study provides an essential basis for manufacturers to optimize the process parameters of rutin raw materials.

New adamantane-containing derivatives of edaravone, one of two drugs used to treat amyotrophic lateral sclerosis, were synthesized. The pyrazolone ring and adamantane moiety in the new edaravone derivatives were conjugated by alkyl and azetidine linkers via amination of the corresponding alcohol mesylates. Some of the new compounds were found to be effective blockers of the allosteric NMDA receptor binding site in rats but exhibited little activity against the intrachannel NMDA receptor binding site. The structure–activity relationship between the ability to block the ifenprodil binding site and the structure of the linkers and substituents on the molecule was analyzed.

Varieties of Mentha piperita L. (peppermint) cultivated at altitudes of 1100 and 1650 m above sea level on identical soils were studied to identify the variability in the accumulation and constituent composition of their essential oils. Essential oils from cultivated samples were obtained by hydrodistillation. The composition of volatile organic substances was determined by GC-MS using a Shimadzu GCMS-QP2010 Plus quadrupole gas chromatograph-mass spectrometer. As a result, up to 58 constituents were identified, including 11 major ones. The quantitative content of the essential oil was found to be highly dependent on the climatic conditions of cultivation, whereas the composition of volatile organic substances varied insignificantly for a certain variety but was highly variable between different varieties.

The article touches the most relevant aspects of the role of quality management systems (QMSs) in the creation and replenishment of universal bases of reference materials (RMs) and harmonization of international standards. The article demonstrates how application of a QMS in this area ensures high-quality RM production by controlling the quality at each stage of the technological process. The publication focuses on the potential of a QMS to minimize errors and risks associated with the production of RMs, which increases their reliability and accuracy when used in scientific and production areas.

The optimal diuretic doses of quercetin and rutin (5 mg/kg) and dihydroquercetin and hyperoside (1 mg/kg) were determined in experiments on white rats with a single intragastric administration. The mechanism of action of sodium quercetin and its derivatives on glomerular filtration and tubular transport was studied in acute experiments. Quercetin, dihydroquercetin, rutin, and hyperoside with a single intramuscular injection at the above doses contributed to an increase in diuresis, saluresis, creatinine clearance (except for rutin), and excreted sodium fraction by an average of 141%, 203%, 153%, and 189%, respectively (p < 0.05). Rutin also led to a decrease in the creatinine concentration index (by an average of 79%, p < 0.05). The diuretic furosemide with a single intramuscular injection at the threshold dose of 1 mg/kg increased diuresis, saluresis, and excreted sodium fraction (by an average of 187%, p < 0.05), like the effect of the quercetin derivatives; decreased the creatinine concentration index (by an average of 62%, p < 0.05); and did not affect creatinine clearance identically to the effect of rutin.

In this study, two polyelectrolytes, chitosan and propyl methyl cellulose carbonate, were associated by crosslinking with tripolyphosphate (TPP), to prepare microspheres loaded with amlodipine besylate (Aml). The formulations were optimized by Box–Behnken experimental design, in which three factors, four responses were studied to check the effect of independent variables (concentration of TPP, pH of TPP solution, and pH of a polymer mixture) on responses: zeta potential, particle size, polydispersity index and entrapment efficiency. The optimal encapsulation efficiency was around 92.43%, the zeta potential on average 41.75 mV, and the minimum mean particle size was 310 nm. The effects of the parameters on changes in structure, crystallinity, and surface charges of polymers, by crosslinking in microparticles, were identified by FT-IR, XRD, and dynamic light scattering analyses. The encapsulation parameters and the environment media influenced the mechanism of release and the kinetics model, which was greater in the duodenal medium at pH 5.5 (Q = 100%). The microencapsulation by nontoxic polymers in water is a good method of preparing amlodipine-loaded microspheres, which are intended for the oral route, with optimal dose release in the duodenal medium. This represents the target site for absorption of the drug, in the pulmonary sphere.

A new series of SRC inhibitors based on 7-azaindole core were designed, synthesized and evaluated for antiproliferative and antioxidant activities. All synthesized analogues of 7-azindole were characterized through ¹H and ¹³C NMR and Mass Spectrometry. Synthesized analogues were screened in vitro antiproliferative activity on the MCF-7 breast cancer cell line. Compounds 5a, 5b, 5d, 5g, and 5h showed significant results. Compound 5b was the most active in the series with a GI50 of 2.19 mM. Molecular docking studies of the most active analogues were performed to reveal the structural features responsible for their interaction with the active site of SRC. The synthesized analogues were also screened for antioxidant activity by the DPPH method. In conclusion, for the creation of novel drugs, these compounds offer promising potential.