ScienceRise: Pharmaceutical Science

Study of some properties of hydrophilic ointment bases depending on their composition

2025-09-19T11:06:38+03:00

The aim. To study the properties of multicomponent hydrophilic ointment bases.

Materials and methods. The study focused on hydrophilic bases with varying formulations and ointments containing ofloxacin. The rheological properties of the bases were studied using rotational viscometry, and water absorption and ofloxacin release were investigated using diffusion through a semipermeable membrane. The water content was determined by the semi-micro method, and the ofloxacin content was determined by liquid chromatography. Four spin probes were utilized in the experiment, and the EPR spectra of these spin probes in a mixed solvent PG – M400 and bases were obtained. The type and parameters of the EPR spectra were evaluated. Surface tension was measured using the maximum bubble pressure method, and antibacterial activity was assessed by the agar diffusion method.

Results. The rheological parameters of hydrophilic bases are contingent on the ratio between macrogol 1550 (M1500) and poloxamer P338 (P338), as well as between macrogol 400 M400 and propylene glycol (PG), water content, temperature, and shear stress. It was demonstrated that P338 increases the surface-active properties of bases. The water absorption capacity of the base containing solely a mixture of macrogols is approximately 1.2 times higher than that of the base, which also contains P338 and PG. The release rate of ofloxacin is shown to increase with an increase in PG content, but it is unaffected by the replacement of Proxanol 268 with P338. The incorporation of macrogol 20 cetostearyl ether (M20CSE) and cetostearyl alcohol (CSA) markedly retards water absorption and the release of ofloxacin, and also increases the rheological parameters of the bases. It was demonstrated by the spin probe method that, within a non-aqueous medium, no aggregates are formed from molecules of P338, as well as surfactant and CSA molecules. The PG content affects the growth inhibition zones of P. aeruginosa. The antibacterial efficacy of ointments containing fluoroquinolones against resistant clinical bacterial strains was found to be enhanced by hydrophilic bases.

Conclusions. The rheological parameters of hydrophilic bases can be controlled by modifying the ratio between consistency factors and dispersion medium components, by varying water content, temperature, and shear stress, as well as by adding surfactants and CSA to their formulations. Hydrophilic bases are able to absorb water and they promote the release of ofloxacin. Surfactant and CSA have a significant impact on these processes, reducing their rates. The formation of aggregates from P338 molecules, as well as molecules of surface-active substance and CSA, was not observed in the hydrophilic bases. PG, when incorporated into hydrophilic ointments containing ofloxacin, enhances their antibacterial efficacy

Composition, chemotypes and sub-chemotypes of essential oils from Coriandrum vulgare and Carum carvi fruits cultivated in different countries

2025-10-21T17:24:03+03:00

Coriandrum sativum L. and Carum carvi L. of the Apiaceae family are among the most cultivated plants, as they have been used for a long time as spices and essential oil (EO) bearing plants.

The aim. The aim from of this work is to examine the composition of EOs from commercial samples of C. sativum originating from 6 countries and C. carvi EOs from 2 countries, to establish the variability of the content of their components and to identify possible chemotypes of this species.

Materials and methods. The EOs were hydrodistilled from the dried fruits of C. carvi and C. sativum, and their chemical composition was determined using GC/MS. Samples were obtained from retail pharmacies in 6 different countries.

Research results. In the samples of coriander EOs, 50 compounds were detected. The dominant group of compounds is acyclic monoterpenoids, ranging from 67.3% (Turkey) to 84.2% (Czech Republic). The dominant component is linalool (61.6% – 77.9%). According to the content of the dominant major and minor components, it has been established for the first time that the studied samples of linalool-chemotypes can be divided into several sub-chemotypes. It has been noted for the first time that phenolic monoterpenoids were found in samples from subtropical and tropical countries. There is a strong negative correlation between the content of linalool and α-pinene (-0.891); linalool and γ-terpinene (-0.895). In the samples of C. carvi EOs, 28 compounds were detected. Both studied samples of caraway fruits contain the maximum amount of carvone (54.6% – 66.8%), followed by the content of limonene (19.9% – 30.1%). The EO of the caraway studied samples consists almost entirely of monocyclic monoterpenoids.

Conclusions. The results of our study of coriander fruits essential oil from six countries allowed us to establish its linalool chemotype, which is divided into five subtypes depending on the secondary compounds, that is novelty for research on possible chemotypes of coriander fruit essential oil. The studied samples of coriander fruits EO do not fully comply with the requirements of the ISO 3516:1997 standard; the content of linalool (Turkey) is slightly below the lower limit in accordance with the requirements. The studied samples of caraway EO slightly exceed the limits of the content of the dominant component carvone (Georgia) and contain significantly less limonene (India) in accordance with the requirements of the ISO 8896-2016 standard

The usage of salts of chaotropic anions for the development of HPLC method for the simultaneous determination of cisplatin and carboplatin in model mixture

2025-10-15T23:00:35+03:00

The aim of the work was to develop an RP-HPLC method for the simultaneous determination of extremely polar and non-UV-absorbing chromophore molecules of cisplatin and carboplatin in a model mixture using salts of chaotropic anions, which can be used for single-analyte determination too.

Material and methods: HPLC analysis was performed using Agilent 1260 and Shimadzu LC-2050C with diode array detector (DAD). Cisplatin and carboplation (purity ≥99% (HPLC)) were supplied from Sigma-Aldrich Chemicals Co. (St. Louis, MO, USA). Used dosage forms: cisplatin «Ebeve» (0.5 mg/ml, Austria) and carboplatin «Ebeve» (10 mg/ml, Austria). All used reagents were HPLC gradient chromatography quality and purchased from Merck Darmstadt, Germany.

Results and discussion: Chaotropic agents enhance retention of basic molecules in acidic mobile phases on reversed-phase chromatographic columns and improve peak shape and symmetry. The chaotropic anions that increase interaction between the basic N-containing analyte and the alkyl chains of reversed-phase ligands, such as C-8 and C-18, are frequently employed to enhance and improve the performance of HPLC methods. The chromatographic analysis of cisplatin and carboplatin presented a unique challenge due to their inorganic structure. The experimentally established optimal chromatographic conditions are: mobile phase - 40 mM KPF₆ buffer solution (pH 2.4) and ACN (95:5), chromatographic column - Luna C18 (100 x 4.6 mm 3 µm), column temperature - 30 °C, flow rate - 0.4 ml/min, detection wavelength - 210 nm. Linearity was assessed using five levels of each of the investigated drugs, where concentration varied in the range of 20–100 μg/mL. The proposed HPLC method is green, as confirmed by the most modern metrics for studying greenness (AGREE, MoGAPI, complex MoGAPI, AGSA, CaFRI and CACI).

Conclusions. In this work, thorough scientific research was carried out with the presentation of HPLC method development for the simultaneous determination of extremely highly polar molecules cisplatin and carboplatin in a model mixture using salts of chaotropic anions. In addition, two studied drugs were quantified using rapid, simple, cost-effective HPLC method approaches

Synthesis, structural characterization and antitumor activity of new chromeno[4′,3′:4,5]thiopyrano[2,3-d]thiazole derivatives

2025-10-21T15:36:39+03:00

The development of heterocyclic compounds with significant biological activity remains a priority in modern medicinal chemistry. The use of cascade domino reactions, such as Knoevenagel condensation combined with hetero-Diels-Alder cyclization, enables the efficient construction of complex structures with potential anticancer properties.

The aim of the study. To synthesize a series of thiopyrano[2,3-d]thiazole derivatives via a cascade Knoevenagel–hetero-Diels–Alder reaction followed by N3-alkylation and evaluate their in vitro antitumor activity in the NCI-60 human cancer cell line panel.

Materials and methods. Structural identification of the compounds was carried out using NMR spectroscopy in DMSO-d₆ with tetramethylsilane (TMS) as the internal standard, and LC-MS analysis with an APCI mass-selective detector. Biological activity was assessed using the NCI-60 screening program, which includes a panel of 60 human cancer cell lines of various origins. Key parameters such as growth inhibition (GI₅₀), lethal concentration (LC₅₀), and cytotoxicity at micromolar concentrations were determined.

Results. A series of thiopyrano[2,3-d]thiazole derivatives were synthesized through a two-step domino Knoevenagel condensation and intramolecular hetero-Diels–Alder cyclization between 4-thioxo-2-oxothiazolidinone and O-alkylated salicylaldehyde derivatives bearing allylic or propargyl substituents. Subsequent N3-alkylation yielded compounds 3.1 (60.0%), 3.2 (67.0%), and 4 (58.0%). Introduction of a piperidine moiety enabled the synthesis of water-soluble methanesulfonate salt 5 (70.0%). Reaction with 2,5-(2-propynyloxy)benzaldehyde led to in situ aromatization and the formation of a stable compound 8. Four compounds were tested for anticancer activity. Compound 8 showed the highest efficacy, causing complete cell death in OVCAR-4 (Ovarian Cancer, LC₅₀ = 29.5 μM) and strong growth inhibition in SR (Leukemia, GI₅₀ = 0.676 μM), 786-0 (Renal Cancer, GI₅₀ = 0.696 μM), A498 (Renal Cancer, GI₅₀ = 0.528 μM), and BT-549 (Breast Cancer, GI₅₀ = 0.666 μM) cells.

Conclusions. The proposed synthetic methodology enables efficient preparation of structurally diverse thiopyrano[2,3-d]thiazole derivatives in high yields. N3-alkylation and incorporation of a piperidine fragment allowed for the synthesis of a water-soluble methanesulfonate salt 5. Among the tested compounds, compound 8 exhibited the most promising cytotoxicity and selectivity towards several cancer cell lines, suggesting its potential as a lead compound for further preclinical development of novel anticancer agents

Spectrophotometric method of quantitative estimation of metformin hydrochloride in tablets

2025-10-21T13:21:07+03:00

In Ukraine, more than one million people suffer from diabetes, and this number increases every year. Metformin is one of the most widely used and most effective hypoglycemic agents for oral administration, available in tablet form with various dosages from multiple manufacturers. In this regard, an important task of modern pharmaceutical analysis is the development of highly accurate, reproducible, accessible, and rapid methods for the quantitative determination of this medicinal product.

The aim of the work is to develop a spectrophotometric technique for the quantitative determination of metformin hydrochloride based on the reaction with bromothymol blue in compliance with the SPhU.

Material and methods. As reagent and solvent, bromothymol blue «Honeywell Fluka», acetone of AR grade and purified water were used. Analytical equipment: Specord 200 spectrophotometer, ABT-120-5DM and Radwag XA 210.4Y electronic scales, Elmasonic E 60H ultrasonic bath, measuring glassware of A class.

Results. A novel, sensitive and simple spectrophotometric method for the quantitative determination of metformin hydrochloride (MFH) in tablets was developed and validated. The proposed method is based on the reaction of the analyte with a sulfophthalein dye, in particular with bromothymol blue, using a mixture of distilled water with acetone (1:50) as a solvent. The final yellow product has a maximum optical density at 404 nm. Regression analysis of the method demonstrated a strong correlation (not less than 0.998) within the concentration range of 5.20–7.80 μg/mL. Intra-laboratory precision confirmed the absence of interference from excipients and proved the reproducibility of the method within the selected concentration range. The purposed method is accurate, precise and sensitive, so that it is valuable for routine quality control of MFH in solid dosage forms

Targeted structural design of molecular scaffolds for dual-action peptidomimetic inhibitors against SARS-CoV-2 MPRO and PLPRO

2025-08-22T07:43:45+03:00

The two proteases of SARS-CoV-2 coronavirus – the main protease (M^pro or 3CLpro) and the papain-like protease (PL^pro) – are essential enzymes required for the successful replication of the virus within cells. Both proteases have become major targets in the development of antiviral drugs against SARS-CoV-2. The potential to achieve a dual inhibitory effect has sparked significant interest in creating dual inhibitors as complex therapeutic agents for this virus. In this article, we discuss the development and in silico evaluation of a series of new peptidomimetic molecules designed as dual-action inhibitors of both SARS-CoV-2 M^pro and PL^pro, along with their synthesis. We implemented a combined approach that began with developing a basic molecular model, considering the substrate specificity of the active centers of each protease. Through rational in silico design, we created a series of peptidomimetics. Further analysis of how these compounds bound to the active sites of both proteases enabled us to identify several new structural hits, including hydantoin derivatives, as potential dual inhibitors of M^pro and PL^pro.

The aim of the study. This study aims to establish a common molecular framework for designing dual-action inhibitors targeting the SARS-CoV-2 M^pro and PL^pro proteases. The research includes receptor-oriented molecular docking, in silico optimization, and the selection and synthesis of the most active candidate structures for further in vitro experimental studies.

Materials and methods. LigandScout 4.5 software is used for 3D pharmacophore analysis, visualization, and molecular docking. AutoDock Vina 1.1 provides tools for molecular docking. The PLIP (Protein-Ligand Interaction Profiler) web servers are utilized to study molecular binding mechanisms. DataWarrior 6.0 software helps create a library of molecular structures, calculate physicochemical properties, and analyze molecular frameworks. SwissADME web server is used to predict ADME parameters and assess the pharmacokinetic properties of small molecules as potential drugs.

Results. We analyzed the substrate specificity of the binding sites of the M^pro and PL^pro proteases, which enabled us to identify a common amino acid sequence containing shared recognition elements for both proteases. By rationally modifying the functional groups in this initial base structure, utilizing the principle of isosteric replacement and incorporating non-classical bioisosteres, we developed a series of peptidomimetic frameworks. Molecular docking conducted at the active sites of both M^pro and PL^pro, along with the assessment of their binding energy values (in kcal/mol), identified several structures with potential for dual inhibition. Notably, hydantoin derivatives demonstrated the strongest binding affinity to the active sites of both proteases.

Conclusions. We have identified promising peptidomimetic molecular structures that demonstrate dual inhibitory activity against the SARS-CoV-2 proteases through in silico analysis. Specifically, we discovered a novel class of hydantoin derivatives that act as inhibitors for both SARS-CoV-2 M^pro and PL^pro. The synthesis methods we developed allow for the preparation of these compounds for further in vitro studies

Antibacterial and antibiofilm activity of Albizia lebbeck leaves extracts in Pseudomonas aeruginosa isolated from urinary tract infection

2025-10-28T12:37:34+02:00

Microbial infections have become one of the most pressing public health issues worldwide as a result of the emergence of resistance to current antibiotics. This has prompted scientists to examine the antibacterial characteristics of medicinal plants.

The aim of the study: Extract secondary metabolites from Albizia lebbeck and analyze how they affect Pseudomonas aeruginosa.

Materials and methods: From the labs of the University of Baghdad's Genetic Eng. and Biotech. Institute, 10 isolates of P. aeruginosa were obtained. The identification was confirmed by cultivating the isolates on cetrimide agar and using the VITEK2 technology.

Results: The chemical analysis of the methanolic and aqueous extracts revealed the presence of secondary metabolite molecules such as alkaloids, flavonoids, glycosides, phenols, saponins, and tannins. The total phenols content of the methanolic and aqueous extracts was 71.11 mg/g and 45.15 mg/g, respectively. Furthermore, the results indicated that at a concentration of 50 mg/ml, the methanolic extract outperformed the aqueous extract in free radical scavenging by 78. 65% to 91. 20%. Using the disk diffusion method, the methanolic extract also demonstrated higher antibacterial activity than the aqueous extract of Albizia lebbeck leaves, and its potency increased with increasing concentration. The methanolic extract's lowest inhibitory concentration against P. aeruginosa isolates was determined to be 16 mg/ml, whereas the aqueous extract's was 32 mg/ml. According to the biofilm formation experiment, the methanol extract inhibits the formation of biofilms at a concentration of 200 mg/ml, whereas the aqueous extract does so at a concentration of 400 mg/ml.

Conclusion: This work demonstrated that the secondary metabolites extracted from Albizia lebbeck leaves have a considerable antibacterial and antibiofilm action on P. aeruginosa, even though the bacterial isolates create a strong biofilm. This research has shown that Albizia lebbeck leaves can be used in traditional therapy for bacterial infections and diseases caused by oxidative stress since they contain therapeutic phytochemicals with strong antibacterial and antioxidant effects

Investigating the potential effect of l-citrulline on PI3K signaling pathway: in silico and in vitro evaluation

2025-10-27T16:24:42+02:00

Insulin resistance is a key feature of type 2 diabetes mellitus (T2DM), resulting from dysfunction in the insulin signaling pathway, which involves critical proteins such as IRS-PI3K-IRS-1-PKC-AKT2 and GLUT4. Metformin, a first-line T2DM treatment, exerts its effects via various mechanisms, but alternative therapies are needed. L-Citrulline, an amino acid with antiglycation and antioxidant properties, has shown potential as a therapeutic agent.

The aim. This study aims to evaluate the efficacy of L-Citrulline, alongside the well-established antidiabetic drug metformin, in a T2DM model using both in vitro and in silico approaches.

Materials and methods. Differentiated L6 skeletal muscle cells, induced with high glucose and insulin concentrations to model insulin resistance, were treated with either L-Citrulline or metformin. The expression of PI3K, a key protein in insulin signaling, was assessed using an ELISA Kit. In silico molecular docking studies were also conducted to examine the binding interactions of L-Citrulline and metformin with PI3K.

Results. L-Citrulline treatment significantly increased PI3K concentration levels in insulin-resistant skeletal muscle cells, indicating a potential restoration of insulin signaling. The enhancement in PI3K concentration was comparable to that observed with metformin, validating the effectiveness of L-Citrulline in modulating the PI3K pathway. Molecular docking studies revealed that L-Citrulline formed stable and favorable interactions with PI3K, suggesting strong binding affinity and potential enhancement of its catalytic activity.

Conclusion. L-Citrulline demonstrates potential in modulating the PI3K signaling pathway based on both in vitro and in silico findings, indicating a possible role in improving insulin responsiveness in type 2 diabetes mellitus (T2DM). Nevertheless, these results are preliminary, and further in vivo and clinical investigations are needed to confirm its therapeutic relevance

Thiazolidinone-based compounds as dual-purpose therapeutics: antimicrobial efficacy, cytotoxicity and pharmacokinetic potential

2025-10-29T14:54:57+02:00

Infectious diseases and cancer remain leading global health challenges, with rising resistance to existing antibiotics and limited selectivity of many cytotoxic agents. Heterocyclic scaffolds, particularly thiazolidinones, offer a promising platform for the development of novel antimicrobial and anticancer compounds.

The aim of the study. To evaluate the antimicrobial and cytotoxic properties of thiazolidinone-based compounds against a panel of pathogenic microorganisms and human cancer cell lines, and to identify the most promising derivatives with favorable safety, pharmacokinetic, and mechanistic profiles through molecular docking and dynamics studies.

Materials and methods. A library of 5-enamine(hydrazine)-4-thiazolidinone derivatives was screened for antimicrobial activity against Gram-positive and Gram-negative bacteria and Candida albicans, and for cytotoxic activity against six human cancer cell lines. Minimum inhibitory concentrations (MIC) were determined, and IC₅₀ values were measured for selected compounds. Pharmacokinetic properties, including gastrointestinal absorption and lipophilicity, were assessed in silico. To investigate potential mechanisms of antibacterial action, molecular docking was performed against MurB (UDP-N-acetylenolpyruvylglucosamine reductase) and DNA gyrase subunit B (ATPase domain), followed by molecular dynamics (MD) simulations to evaluate the stability of the most promising complexes.

Results. Thirty-two compounds exhibited antimicrobial activity (MIC ≤ 200 µM), and ten (6, 7, 10, 12, 13, 16, 19, 21, 22, and 29) were identified as the most active. Compound 29, an isatin–oxadiazole hybrid, demonstrated potent activity against Enterococcus faecalis and vancomycin-resistant E. faecium (MIC = 3.13 µM), outperforming vancomycin. Compound 21 was highly active against Staphylococcus epidermidis (MIC = 1.56 µM), while compound 6 showed efficacy against methicillin-susceptible and -resistant S. aureus (MIC = 6.25 µM). Moderate antifungal activity was observed for compound 27 (MIC = 100 µM), whereas Gram-negative bacteria were largely resistant. Cytotoxicity screening revealed selective anticancer activity of compounds 12 and 27, with high therapeutic indices against CCRF-CEM cells and minimal effects on normal fibroblasts. Compound 2 exhibited strong cytotoxicity (IC₅₀ = 1.1 µM), while compound 29 combined non-cytotoxicity with favorable pharmacokinetic characteristics.

Molecular docking supported MurB as the primary antibacterial target, with the most active compounds (21 and 29) showing the most favorable binding energies. Compound 29 also exhibited strong affinity for GyrB, indicating a potential dual-target mechanism. Molecular dynamics confirmed that MurB–compound 29 complexes were particularly stable, correlating well with experimental antibacterial activity.

Conclusions. Thiazolidinone-based hybrids demonstrated promising antimicrobial and anticancer properties. Compound 29 emerged as a particularly attractive dual-purpose candidate due to its potent activity, safety profile, favorable pharmacokinetics, and validated interaction with essential bacterial enzymes. Together, biological and computational results support the potential of thiazolidinone scaffolds as a basis for the development of selective or multitarget therapeutic agents

Pharmaceutical cream with Carthamus tinctorius L. extract: formulation and evaluation

2025-10-29T15:53:01+02:00

The aim. The aim of this study was to develop and evaluate a pharmaceutical cream formulation containing a liquid extract of Carthamus tinctorius L. flowers. The research focused on characterizing the extract using instrumental analytical methods (IR spectroscopy, spectrophotometry with rutin standard, HPLC, and UV spectroscopy for β-carotene) and on designing cream bases with different hydrophilic, hydrophobic, and emulsion components. The study further sought to assess the quality parameters of the developed formulations, including appearance, homogeneity, thermostability, colloidal stability, and pH, in order to identify the most stable and pharmaceutically promising compositions.

Methods. A liquid extract of Carthamus tinctorius L. flowers was used as the active pharmaceutical ingredient. Its composition and properties were analyzed using IR spectroscopy, spectrophotometry (λmax = 410 nm, rutin standard), HPLC (comparison with rutin), and UV spectroscopy for β-carotene (λmax ≈ 450 nm). Based on the extract, eight cream samples were formulated with different hydrophilic, hydrophobic, and emulsion bases. The quality of the samples was evaluated according to the following parameters: appearance, homogeneity, thermostability, colloidal stability, and pH.

Results. IR spectroscopy confirmed the presence of polyphenols, flavonoids, and organic acids. The total flavonoid content was 2.2% (calculated as rutin). HPLC analysis revealed multiple peaks, including rutin (Rt = 18.17 min), coinciding with the standard (Rt = 18.20 min). The UV spectrum showed a high level of β-carotene (A = 4.35 compared to A = 0.60 in the standard). Out of the 8 cream samples, only formulations No. 3, No. 5, and No. 7 demonstrated stability.

Discussion. Instrumental analysis confirmed the presence of a complex of biologically active substances in the extract, ensuring its anti-inflammatory and antioxidant properties. The high content of flavonoids and β-carotene substantiates the therapeutic potential of the product. Selection of the cream base showed that a rational combination of hydrophilic and hydrophobic components ensures stability and preservation of active ingredients.

Conclusions. A therapeutic-cosmetic cream with a liquid extract of Carthamus tinctorius L. has been developed. Out of 8 tested formulations, samples No. 3, No. 5, and No. 7 demonstrated the best quality parameters and are recommended for further investigation. The obtained data confirm the prospects of using safflower extract in the creation of modern phytopharmaceuticals with pronounced anti-inflammatory and antioxidant activity