The objects of the present study are nanoparticles (NPs) based on a copolymer of lactic and glycolic acids (PLGA), loaded with the anticancer drug doxorubicin (DOX-NP) and histone deacetylase inhibitor vorinostat (SAHA-NP), developed for the breast cancer treatment. Drug encapsulation into PLGA matrix improve drug safety profile and allow to overcome multidrug resistance. In the current study, we developed a high-performance liquid chromatography method for the simultaneous determination of DOX-NP and SAHA-NP using Box-Behnken design, followed by the validation and NPs stability determination after sterilization treatment with γ-irradiation.

The separation was performed using a Nucleodur C-18 Gravity column (250 mm × 4.6 mm × 5 µm). Samples were prepared by precipitating PLGA with dimethyl sulfoxide. Three independent variables were analyzed to determine the most optimal conditions: methanol concentration (0-20%), pH (2.5-4.5) and flow rate (0.8 -1.2 mL /min). We evaluated contributions of these variables to the peak resolution and the retention time of the last peak of the analyte using Box-Behnken design. Next, we simultaneously optimized all dependent variables and established their most optimal values using the desirability function.

The optimized method was accurate, precise and linear in the range of 4.2–52.0 µg/mL for both drugs (R² = 0.9999 for vorinostat and R² = 0.9988 for doxorubicin). γ-irradiation at a dose of 25 kGy resulted in degradation of DOX-NP less than 95%, while the amount of SAHA-NP impurities was 88%.

Thus, the developed method is suitable for simultaneous analysis of DOX-NP and SAHA-NP, including the analysis of impurities.

Funding: This study was supported by the Russian Science Foundation research grant No. 22-25-00293, https://rscf.ru/project/22-25-00293/

The study examined how well the alkaloid content of Vitex doniana affected the liver function in albino rats. The liver damage in albino rats was induced using a CCl₄ solution in paraffin (1:1). The liver function tests were performed by administering several groups of albino rats oral dosages (200, 400, and 600 mg/kg) of the bulk alkaloid over the course of 14 days, After the rats were sacrificed, the liver was examined hepatopathologically to determine the serum levels of albumin, total protein, cholesterol, triglycerides, low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs). When compared to the control, the alkaloid fraction of V. doniana significantly (p ˂ 0.05) enhanced the levels of total protein, serum albumin, and HDLs. The findings also demonstrated that rats administered with alkaloid fraction had significantly (p ˂ 0.05) lower serum levels of CHOL, TAG, LDLs, and BUN as compared to untreated rats. The alkaloids repaired the normal cellular architecture of the liver that had been damaged by the standard hepatotoxin. The use of V. doniana in treating disorders linked to the liver is supported by the fact that its alkaloids repair CCl₄-induced hepatocellular damage.

Ethnopharmacological relevance: Phytotherapy has been playing a significant role in the livestock health care system for a long, especially in remote areas. This study aimed to document the therapeutic uses of plant species practised by the Rif's indigenous people to treat various veterinary health diseases.

Methods: Semi-structured questionnaires, field walks, and group discussions were conducted from June 2016 - to October 2019 to collect the data. Quantitative indices include Plant Part Value (PPV), Use value (UV), Fidelity Level (FL), Relative Popularity Level (RPL), Rank Order Priority (ROP), Jaccard Index (JI), and Informant Consensus Factor (ICF) were used for the data analysis.

Results: A total of 300 medicinal plants belonging to 205 genera and 67 families have been recorded with ethnoveterinary uses. Dominant families are Asteraceae (33 species), Lamiaceae (28 species), and Fabaceae (24 species). The reported illness was classified into 4 disease categories based on ICF values, and the highest number of plants was reported to treat internal parasites (ICF=0.967). Leaves were the most consistently used parts (PPV=48.4%). Aloysia citrodora Palau. (RPL=) had the highest RPL level (1.15).

Conclusions: It can be concluded that the local people of Rif hold rich ethnoveterinary knowledge to cure livestock diseases. Plant species with high FL, RPL, and UV values should be screened for comprehensive phytochemical and pharmacological studies to validate the ethnomedicinal knowledge.

Nitrogen-containing heterocycles can have several applications in the pharmaceutical industry, since they contain a wide spectrum of biological activities. Imidazolidinones have shown activity against leukemia, lung cancer and metabolic disorders. These cyclic urea frameworks can be obtained through transition-metal-catalyzed intermolecular cycloaddition using an aziridine moiety as starting material. These reactions often provide effective one-step procedures that result in heterocyclic derivatives, that are challenging to access through conventional approaches.

We have previously described the photoreaction of butyl pyridinium salt into the corresponding bicyclic aziridine under continuous-flow. Additionally, we reported that palladium-catalyzed ring opening of bicyclic aziridines with active methylenes thought a new S_N2’ selectivity. In this study, is presented the reaction between bicyclic aziridines and several isocyanates, in the presence of Pd(0)-catalyst. The reactions proceed through ring opening of the aziridine moiety, with the formation of the π-allylpalladium complex, followed by cyclization via nucleophilic addition of nitrogen to the isocyanate, affording regioselectively imidazolidinones.

Transforming Growth Factor- β Receptor type 1 (TGF-βR1) is an important anticancer target involved in promoting cell proliferation, progression and metastasis through induction of angiogenesis and suppression of immunological responses during the late stage of malignancy. Tranilast was initially approved for the treatment of bronchial asthma and allergic conditions in 1982. Later, it was revealed that Tranilast has numerous effects on cancer hallmarks, including immune evasion and sustained proliferation via inhibition of TGF-βR1. This research describes the design of a novel series of anthranilate derivatives having various modes of interactions with TGF-βR1 compared with Tranilast. A database of novel Tranilast analogues was generated using MOE software using Fragment-Based Drug Design. Representative compounds were selected from the database and docked in the identified binding site of TGF-βR1. Several compounds showed higher binding affinity for TGF-βR1 compared with the lead compound in this work, Tranilast. Compounds with high docking scores contained a positively charged amine group that interacted with Asp290 or a negatively charged carboxylate group with Lys 335 in the TGF-βR1 ATP binding site. Also, compounds containing an aromatic group showed high docking scores through interacting with Ser287, Lys337 or Ile 211. Compounds A11, A14, A16, and B5 which had the best poses in terms of binding interactions and docking scores to the binding site will be considered for further synthesis and biological evaluation.