Liver cancer is the malignancy with the highest mortality rate among digestive system cancers worldwide. Flavonoid plant extracts have shown significant safety and extensive function, especially anti-tumor activity. In this study, the therapeutic effects of a combination of baicalein and luteolin were evaluated in vitro. Cell proliferation, migration, and apoptosis were performed respectively through MTT assay, clone formation, wound healing, transwell, and JC-1 staining. Protein levels of EGFR, p-ERK, NFκB, and cleaved-caspase3 via western blotting and the interaction with key proteins EGFR and NFκB by molecular docking were determined in order to explore the underlying mechanism. In addition, a mouse heterotopic transplant tumor model was established to assess the anticancer activity in vivo. The experimental results showed that the combination of baicalein and luteolin exhibited more potent in suppressing cell proliferation and migration and inducing cell apoptosis when compared with baicalein or luteolin. The western blot and molecular docking studies demonstrated that the potential mechanism may relate to the inhibiting of the EGFR/NFκB signaling pathway. Moreover, the HepG2 cell xenograft model, hematoxylin and eosin, and immunohistochemical staining results also confirmed that the combination of baicalein and luteolin was more effective than a single compound in inhibiting tumor growth. In summary, the combination of baicalein and luteolin may resist the proliferation, migration, and apoptosis activity of HepG2 cells through the EGFR/NFκB signaling pathway, which provides new insights for further exploring plant extract treatment for liver cancer.
HPLC techniques for quantitative determination of myricitrin (myricetin-3-O-α-L-rhamnopyranoside) in extracts from leaves of common myrtle (Myrtus communis L.) were developed. The contents of myricitrin in tincture, infusion, and thick extract of myrtle leaves were determined as 0.68 ± 0.02; 0.17 ± 0.01 and 12.75 ± 0.05
The use of sunscreen is essential to protect the skin from the acute and chronic effects of UV rays. This study was aimed at investigating in vitro evaluation of photoprotection, cytotoxicity, and phototoxicity of extracts from Golnar-e-farsi, saffron, and true indigo. The plant extracts were prepared using the maceration method. The in vitro evaluation showed that the sun protection factor (SPF) of the barrier cream containing 1
The 18-kDa translocator protein (TSPO) is a key target of research aimed at understanding the mechanisms of neuroinflammation and stress-associated disorders. TSPO ligands exhibit significant therapeutic potential, including anxiolytic, antidepressant, and neuroprotective effects, making them promising for new drug development. However, the mechanisms of TSPO interaction with various ligands require more detailed studies using modern molecular dynamics methods, which were used in the present work to study the molecular interactions of the TSPO protein (PDB ID: 2MGY) with its promising ligands GML-1 and GML-3, including a comparative analysis with known TSPO ligands PK-11195, Ro5-4864, and etifoxine. The study was conducted using the Schrodinger software package (version 2024-2). The analysis included evaluations of the RMSD, RMSF, binding free energy (∆G), hydrophobic interactions, hydrogen bonds, and other types of molecular contacts. The ligands GML-1 and GML-3 demonstrated high structural stability in complexes with TSPO protein (RMSD: 1 – 3 Å) and favorable binding free energies (∆G ≈ –69.74 and –67.68 kcal/mol, respectively), comparable to those for PK-11195 and etifoxine. Interaction analysis showed that GML-1 and GML-3 formed stable hydrophobic contacts and hydrogen bonds with key amino acid residues of TSPO protein such as TRP_107, LEU_49, and VAL_26, which played important roles in stabilizing the complex. Compared to known ligands, GML-1 and GML-3 provided similar structural stability and binding energy, while demonstrating high stability of the complex in molecular dynamics. These properties make them promising targets for further research and development of drugs that modulate TSPO activity.
The physicochemical properties of polysaccharides from leaves of the common horse chestnut (Aesculus hippocastanum L.) grown in the Republic of Uzbekistan were isolated and studied. Water-soluble polysaccharides were extracted in 13.5
The aim of the present work was to investigate the general toxicity, local irritant effects, and antiallergic activity of a transdermal therapeutic system (TTS) based on micellar desloratadine. The desloratadine-containing TTS exhibited an antihistamine effect for 14 days in an allergic reaction model and prevented the development of allergic rhinitis when rats were sensitized with ovalbumin. A study of the general toxicity and local irritant effects of the TTS compared to Vaseline showed that the TTS affected the biochemical and hematological parameters in rats less than the reference drug Vaseline. Application of the TTS to the skin of rats for 14 consecutive days had no significant effect on respiratory or cardiovascular functions. The TTS did not cause local irritation with repeated skin application and did not alter the skin morphology.
The effect of new progestins of the D′-pentarane series containing an additional three- or six-membered D′ ring in the 16α,17β-positions of the steroid skeleton and oxime groups in the 3- or 6-position on the expression level (amount of mRNA) of genes of progesterone- (mPR, PGRmC1, PR-A, PR-B) and estrogen-steroid (mER, ERα, ERβ) and vitamin D receptors in immunocompetent blood cells of healthy patients was studied. Only pentarane 6(E)-hydroxyimino-16α,17β-cyclohexanopregn-4-en-3β-ol-20-one (K-1044) of the four steroids studied with high progesterone receptor binding did not reduce the level of estrogen receptor ER mRNA, a predictor of the effectiveness of menopausal hormone therapy. The remaining three compounds exhibited pronounced inhibition of ER mRNA expression by 3.5 and 9 times lower than the control values for 6(E)-methoxyimino-16α,17β-cyclohexanopregn-4-en-3-ol-20-one (K-1046) and 16α,17β-cyclopropano-pregn-4-ene-3,20-dione (K-338), respectively, and practically to zero for 3(E)-hydroxyimino-16α,17β-cyclo-hexanopregn-4-ene-3,20-dione (K-993). Also, these four pentaranes not only did not reduce but also increased the expression of vitamin D receptor (VDR) mRNA in peripheral blood mononuclear cells. The effect of pentarane K-1044 was the most significant.
Several drugs with coatings based on methacrylic acid-ethyl acrylate copolymers, which should be stable in acidic medium, were experimentally found to dissolve at pH 4.5. The non-stoichiometric composition and microstructure of these methacrylic acid-ethyl acrylate copolymers with different solubilities were comparatively analyzed by NMR to understand the reason for this phenomenon. Astructural interpretation of the PMR and 13C NMR spectra of methacrylic acid-ethyl acrylate copolymer was presented. The mass fractions of methacrylic acid were estimated by PMR for 10 samples; the microstructure of the copolymers, by 13C NMR. The different dissolution profiles of these samples were found not to be related to their structural specifics. It was suggested that the instability of the drug coating at pH 4.5 was due to a noncompliance of the technological process for its application or a deviation of the average copolymer molecular mass from the nominal value.
The review systematizes our studies over the past 10 years on the search for new synthetic α-amylase inhibitors obtained by diversity-oriented synthesis (DOS) based on multicomponent reactions of CH-acids with formaldehyde and S- or N-nucleophiles. The DOS strategy turned out to be a rational way to design sulfanylmethylazoles and oxazine derivatives of phenol and their metal complexes. Evaluation of the inhibitory activity of α-amylase in vitro and in silico showed that inhibition occurs by competitive, noncompetitive, and uncompetitive mechanisms, depending on the structure of these groups of compounds. Water-soluble complexes of palladium with a sulfanylmethylisoxazole ligand and copper with an aminomethylphenol ligand showed higher inhibitory activity against α-amylase than the reference drug acarbose.
Osteoarthritis is a prevalent degenerative joint disease characterized by the progressive loss of articular cartilage and is one of the leading causes of disability worldwide. Current treatment options for osteoarthritis remain limited, primarily consisting of symptomatic treatments such as intra-articular injections of glucocorticoids and hyaluronic acid preparations. Among the most commonly used corticosteroids for osteoarthritis treatment are betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BD). Accurate identification and quantification of these corticosteroids in pharmaceutical formulations are essential to ensure compliance with analytical and regulatory standards. Thus, in this study a simple high-performance liquid chromatography method (isocratic method) has been developed and validated for the simultaneous determination of BSP and BD. Discovery® HS C18 Column (250, 4.6 mm, 5 μm) was used at 35°C. The mobile phase was prepared using a mixture of acetonitrile:water (75:25 v/v) containing 0.1
This article presents validation of a quantitative determination method for SS-68, an indole derivative that is of interest for further study to conduct more in-depth research and potential clinical implementation as an antifibrillatory antiarrhythmic agent.
This review article discusses the different analytical techniques available in the literature for determining the concentrations of five different drugs, namely molnupiravir, dolutegravir, remdesivir, ledipasvir, and sofosbuvir, in pharmaceutical and biological samples. The methods discussed include the UV-visible method, HPLC, spectrofluorometry, near-IR spectroscopy, polarography, voltammetry, capillary electrophoresis, and hyphenated techniques include LC-MS, LC-MS/MS UPLC-MS/MS, and GC-MS. The article also provides a comparative analysis of the different analytical techniques and their respective advantages and limitations for the estimation of these drugs.
Polycystic ovary syndrome (PCOS) is a multifaceted endocrine-metabolic disorder that not only leads to reproductive complications but also adversely affects other systems of the body. Ovarian fibrosis is considered to be one of the pathological mechanisms of PCOS. The purpose of this research was to explore whether traditional Chinese medicine monomers kaempferol can improve the epithelial-mesenchymal transition of ovarian stromal cells and the mechanism of its effect. The ovarian stromal cell fibrosis model was induced by cisplatin and divided into four groups. Immunofluorescence technology was applied to identify ovarian stromal cells, molecular docking method was applied to screen potential effective monomers, CCK8 method was used to detect cell viability in each group,Western Blot and RT-PCR were used to detect the expression of fibrosis-associated factors in the cell model, and TGF - β1/Smad3 pathway-related factors were experimentally verified. Compared with the control group, the protein expression levels of α-SMA, TGF- β1, TGFBR1, Smad3, and p-Smad3 in the cisplatin group were significantly increased (P < 0.05), and the mRNA levels of α-SMA, TGF- β1, and ALK5 were significantly increased (P < 0.05). Compared with the cisplatin group, the protein expression of α-SMA, TGF- β, TGFBR1, Smad3, and p-Smad3 in the low-dose and high-dose kaempferol groups was markedly decreased (P < 0.05), and the mRNAlevels of α-SMA, TGF-β1, and ALK5 was noticeably decreased (P < 0.05). Kaempferol may inhibit the epithelial-mesenchymal transition of ovarian stromal cells by regulating the TGF- β1/Smad3 signaling pathway.
The anti-inflammatory and antiulcer activity of several glycyrrhizic acid (GA) conjugates with amino-acid methyl/ethyl esters at a dose of 50 mg/kg was studied in a carrageenan-induced paw edema model in mice as compared with voltaren and in an indomethacin-induced gastric ulcer model in rats as compared with omeprazole. The GA conjugate with L-alanine ethyl ester (V) exerted a pronounced anti-inflammatory effect comparable to voltaren, reducing paw edema by 1.8 times (p < 0.01) as compared with the control group and by 1.5 times (p < 0.01) as compared with GA. The highest antiulcer activity, comparable to that of omeprazole, was demonstrated by the GA conjugate containing three residues of L-methionine methyl ester III and the GA conjugate with two residues of aminoenanthic acid methyl ester VII, reducing the number of ulcers as compared to the control by 3.9 times (p < 0.001) and 3.7 times (p < 00.001), respectively. These conjugates reduced the number of ulcers by an average of 3.1 times (p < 0.01) as compared to starting GA.
Isotopically labeled compounds have played and continue to play a significant role in biological research. A new stage in their use is currently emerging, unique in that deuterium compounds are being offered as pharmaceuticals. The chemistry of isotopically labeled compounds is evolving into medicinal chemistry. The synthesis of deuterium-based drugs is becoming a pressing issue. The present review examines various approaches to producing deuterium drugs such as deuterium introduction by heterogeneous isotope exchange using D2 and D2O; synthesis of labeled compounds using labeled reagents, labeled precursors, and homogeneous catalysts; and deuterium introduction using chemical synthesis.
Phacelia tanacetifolia Benth. (Boraginaceae) is an unpretentious melliferous plant species that is widely cultivated as a cover crop. Spectrophotometric analysis of eight Russian varieties of P. tanacetifolia revealed the presence of flavonoids (0.96 – 3.25 mg/g) and phenylpropanoids (1.53 – 15.69 mg/g) in the herb of this species. Liquid chromatography mass spectrometric studies identified 47 phenolic compounds, including caffeoylquinic and feruloylquinic acids; caffeic acid depsides; glycosides of isorhamnetin, quercetin, kaempferol, luteolin and apigenin; and hydroxycinnamoyl conjugates of spermidine and putrescine, most of which were new for the species. Chromatographic separation of the BuOH extract of P. tanacetifolia isolated a new compound (phaceliaside) that was N1,N5,N10-tri-O-(EEE)-p-coumaroyl spermidine 4′′-O-β-Dglucopyranoside, the structure of which was elucidated using UV and NMR spectroscopy and mass spectrometry. Quantitative analysis data indicated a high content of flavonoids (up to 3.61 mg/g), hydroxycinnamates (up to 5.71 mg/g), and phenolamides (up to 9.50 mg/g) in the herb of P. tanacetifolia. The effect of individual compounds on the activity of three tyrosinases was studied. It was shown that phenolamides, including N1, N10-di-O-(EE)-p-coumaroyl-N5-O-(E)-caffeoyl spermidine, N1,N10-di-O-(EE)-p-coumaroyl putrescine, and N1,N5,N10-tri-O-(EEE)-p-coumaroyl spermidine, effectively inhibited human tyrosinase. The studies showed that P. tanacetifolia is a source of various phenolic compounds with antityrosinase activity.
A simple capillary zone electrophoresis (CZE) version suitable for fast and efficient quantification of 25Mg2+-carrying porphyrin-fullerene cation-exchanger nanoparticles in rat brain tissue carried out during preclinical studies of this type of novel nanoprotectors was proposed. The potential application of this technique for resolving pharmacokinetic tasks is under discussion with the emphasis on a comparison to the routine protocol chromatographic procedures (HPLC, TLC, etc.).
Ritter reactions between dialkylbenzylcarbinols and HCN, (1-naphthyl)acetonitrile, or diphenylacetonitrile yielded the corresponding 6,7-(R1O)2-3,3-(R2)2-3,4-dihydroisoquinolines, 1-(1-naphthylmethyl)-6,7-(R1O)2-3,3-(R2)2-3,4-dihydroisoquinolines, and 1-benzhydryl-6,7-(R1O)2-3,3- (R2)2-3,4-dihydroisoquinolines (R1 = OMe, OEt; R2 = Me, Et), a total of eight compounds. The hydrochlorides of the obtained compounds were tested for four types of activity. The LD50 values of the tested substances (mice, intravenous) ranged from 30.0 to 70.8 mg/kg. Three substances exhibited antiarrhythmic activity with antiarrhythmic indices of 1.8 to 2.1. Three of the eight substances reliably demonstrated weak anticoagulant activity (14.3 to 23.2
The cytotoxic and antioxidant activity of 1,2,3,4-tetrahydropyridine-3,5-dicarboxylic acid (TDA) derivatives obtained by Mannich reactions of ethyl acetoacetate or ethyl 4,4-difluoroacetoacetate with formaldehyde and primary amines, including amino acid esters, was studied. The most active cytotoxic compound was fluorinated TDA with a tyrosine fragment, which showed a cytotoxic effect on HTC116 human colorectal carcinoma cells (IC50 70.25 μM). N-Propyl- and N-2-[(2-hydroxyethyl)amino]ethyl-TDA exhibited antioxidant properties in the FRAP model (EC50 12.03 and 11.83 μg/ml) that were comparable to those of ascorbic acid and Trolox.
A method using UV spectrophotometry for the quantitative determination of a new biologically active compound with antihypoxic activity, 2-ethyl-6-methylpyridinol-3-yl thiooctanoate, was developed. The method was validated for specificity, linearity, analytical detection range, accuracy, and precision. It was found to meet the requirements for pharmaceutical analysis methods.
