Vol 53, No 5 (2019)

2-Adamantylaminopropanol hydrochloride (ADK-971) and 5-hydroxyadamantan-2-ylaminopropanol hydrochloride (ADK-1013) were less active than hemantane in parkinsonian syndrome murine models. ADK-971 and AKD-1013, like hemantane at a dose of 20 mg/kg, exhibited comparable antiexudative effects in the mouse acetic peritonitis model. However, ADK-971 and ADK-1013 (20 mg/kg), in contrast to hemantane at the same dose, did not possess analgesic effects against visceral and thermal somatic pain in mice.

According to the literature, iron chelators have been used to inhibit tumor cell proliferation. Hydroxypyridinones, due to easy derivatization and high affinity for iron, have been suggested as an attractive target for the development of iron scavenging ligands. N-arylhydroxypyridinone derivatives as iron chelators have been previously designed and synthesized, and the present study is performed in order to evaluate the antitumor efficacy of these compounds,. Four derivatives of hydroxypyridinone were tested against HCT116 and SW480 colon cancer cell lines for 48 h using MTT assay. One compound (3-hydroxy-2-methyl-1-phenylpyridin-4(1H)-one, PMPO) showed the maximum cytotoxic activity on both HCT116 and SW480 cancer cells with IC₅₀ = 243 and 180 μmol, respectively, for 48 h treatment. The obtained results demonstrated that various concentrations of test compounds exhibited significant reduction of the cell viability (P < 0.05) in a concentration dependent manner. Our findings indicate that the proposed hydroxypyridinone derivatives can be considered as a new option for the treatment of colon cancer.

There is a method to employ aberrant levels of mobile ferrous iron (Fe(II)) for selective drug delivery in vivo. This approach makes use of a 1,2,4-trioxolane moiety, which serves as an Fe(II)- sensitive “trigger,” making drug release contingent on Fe(II)-promoted trioxolane fragmentation. In this study we focused on the prototype drug conjugate of 1,2,4-trioxolane ring joined via a traceless linker to drug species, which is conjugated to the linker via a free amine or alcohol function to form a complex.We studied four complexes formed of different drugs with various linkers. The structure and physicochemical properties of complexes were studied using the Hartree – Fock method with 6-311++G** basis set. The influence of the oxalan ring and various drugs on the properties of complexes has been studied. Geometric parameter, energies, nuclear chemical shielding constants, direction of dipole moment vector, partition coefficients, electric polarizabilities, and other physicochemical properties of these compounds have been calculated.

New 4-phenylpyrrolidone derivatives were designed from racetam structures that combine nootropic and anticonvulsant activity. The proposed compounds were synthesized using 4-phenylpyrrolidone and aromatic amines. The anticonvulsant activity of the new compounds was studied. The structure–activity relationship was analyzed. The most active compound was the 2,6-dimethylanilide of (2-oxo-4-phenylpyrrolidin-1-yl)acetic acid at doses of 2.5 – 5.0 mg/kg, which surpassed the reference drug levetiracetam at doses of 2.5 – 600 mg/kg in all tests and possessed distinct nootropic activity that was comparable to that of the reference nootropic drug piracetam at a dose of 400 mg/kg.

In the past decade, research in the area of nanodrug delivery has reached a new height with the advent of lipid based nanodrug delivery systems. Lipids being biocompatible and possessing diverse physicochemical properties have tremendous potential to enhance oral bioavailability of water insoluble drugs. Incorporation of a drug in lipid carriers is a smart approach to overcome problems related with conventional oral therapy. In recent years, two lipid based nanoparticles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are widely explored. SLN are spherical nanoparticles with a drug-containing solid lipid core stabilized with surfactants and formulated mainly to improve bioavailability of the drug molecules. Despite several advantages of SLNs, their major drawbacks include limited drug loading, drug leakage, and crystallization during storage. These drawbacks were avoided or reduced by the development of a new generation of lipid nanoparticles, the NLC, wherein a solid lipid is blended with liquid lipid. Modulation of drug release was added advantage with NLC formulations. The present review focuses on production techniques, characterization, release characteristics, stability, toxicity and potential applications of SLNs and NLCs.

Modeling lyophilization is the most convenient approach to optimizing the drying stage because it allows the optimal temperature regime for secondary drying to be selected using a small number of experiments and the duration of the process to be calculated as a function of the conditions. A simple mixed mathematical model of the process was used because of the ability to extrapolate the data and the small number of required experiments. The dependences of the drying rate on thermal variables at a constant total pressure and of the possibility of a dynamic temperature rise on residual moisture content were calculated. The optimal secondary drying regime was determined by comparing the performance of various regimes, verifying the reproducibility of the model, and comparing theoretical and experimental values of residual moisture. The most suitable drying regime for bis(N-monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2) lyophilizates for injection was selected.

Formulas for calculating relative response factors (RRFs) and correction factors (Fs) of impurities and those necessary for understanding the essence of RRFs and Fs are presented. The main methods for determining Fs and their limitations (conditions necessary for correct determination of RRFs and Fs) are considered. These limitations do not appear in the European and US pharmacopoeias although they must be considered to determine the correct Fs. Examples and recommendations are given for reliable determination and correct use of the Fs.

A synthetic method for a series of new coumarin conjugates was developed. Their structures and physicochemical properties were determined by modern spectral methods (IR, NMR, ESI-MS). The anticoagulant activity was studied in vivo by determining the prothrombin time (PT). Compounds 4a (PT = 10.88 ± 0.56 sec) and 4b (13.10 ± 3.56 sec) were the most active and comparable to the reference drug warfarin (7.97 ± 1.93 sec).

A complex of biologically active compounds was isolated from Lychnis chalcedonica L. cultivated at the Siberian Botanical Garden at Tomsk State University. HPLC analysis found that the isolated compounds were flavonoids with retention times 10.40, 12.45, 13.29, and 15.47 min. The major flavonoid constituent was vicenin with t_r = 13.29 min and a peak area of 87.4%. The flavonoid complex of L. chalcedonica was studied using three transplanted tumor models, i.e., Lewis lung carcinoma (LLC), melanoma B-16 (B-16), and lung cancer RL-67 (RL-67). Tests on C57BL/6 mice showed that the L. chalcedonica flavonoid complex inhibited development of melanoma B-16. Co-administration of L. chalcedonica flavonoids and cyclophosphamide enhanced the antitumor effect of the cytostatic in animals with B-16, RL-67, and LLC.

The promising antitumor peptides Melanotan II and YSL amide were synthesized for the first time in gram quantities in overall yields of 72 and 50%, respectively, by Ajiphase^® methodology. This method was shown to be promising for peptide manufacturing. The proposed methods are as convenient as polymer-phase syntheses with the reagent consumption and associated analytical simplicity of classical solution syntheses.