A biologically guided isolation of secondary metabolites from Cousinia alata Schrenk wild plant growing in Akmola region, Kazakhstan, led to the isolation of the bioactive diterpene grindelic acid (1). Six flavonoids were also isolated and identified as retusine (2), pachipodol (3), jaranol (4), penduletin (5), casticin (6), and 5, 7, 3-trihydroxy-3, 4-dimethoxyflavone (7). Penduletin (5) showed moderate cytotoxic activity assay. Grindelic acid exhibited promising cytotoxic activity against the Artemia salina nauplii and antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Salmonella enteritidis. The presence of the essential pharmacophoric features of histone deacetylase (HDAC) inhibitors in the structure of grindelic acid encouraged us to run a molecular docking study against the HDAC enzyme to understand its mechanism of action on a molecular level. Grindelic acid showed a binding mode of interaction similar to that of the cocrystallized ligand and exhibited good binding affinity against HDAC with the binding free energy of 18.70kcal/mol. The structures of isolated compounds were determined by MS, 1D, and 2D NMR spectroscopy methods. Compounds (17) were isolated for the first time from Cousinia genus.

The project team synthesized and studied the binary oxide composed of lanthanum and copper, which was characterized using FTIR, XRD, SEM, XPS and BET.

The synthesis of new composite nanomaterials based on graphene oxide (GO)modified with cellulose and its derivatives, as well as nanocellulose, is currently an important direction and contributes toward solving many problems in various fields such as nanotechnology, information technology, medicine, high-dielectric materials, and nanoelectronics. In this work, for the first time, for the production of GO and its membrane with carboxymethylcellulose (CMC), local Kazakhstan “Ognevsky” graphite was used as the initial raw material. In this regard, the preparation of nanocomposites of GO modified with cellulose derivatives, including CMC, attracts great interest from scientists and expands its field of practical application due to the significant changes in its physicochemical properties. In this work, the GO obtained using the Hummers method was modified by CMC, and its physicochemical, structural, and electrical characteristics were studied. The GO/CMC membrane was synthesized by mixing 1% GO with crushed solid mass of CMC (0.03 g; 0.06 g; 0.15 g) and then processing using ultrasound. The surface morphology of the GO/CMC membrane was studied using scanning electron microscopy (SEM). It has been established that by increasing the mass of CMC (0.03 g; 0.06 g; 0.15 g), the polymerization of CMC occurs on the surface of GO nanosheets. Cross-sectional micrographs of GO/CMC show the formation of sandwich-like layered structures. The synthesis efficiency (yield) of GO from synthetic graphite is 10.8%, and GO from Ognevsky graphite is 11.9%, almost 1.1% more than GO from synthetic graphite. The mechanical tensile strength increases from 2.3 MPa to 14.3 MPa and the Young’s modulus from 2.3 MPa to 143 MPa. The electrical parameters of the humidity sensor based on GO and GO/CMC membranes (0.03 g; 0.06 g; 0.15 g) were studied as a function of humidity to determine the performance of the device.

The analysis of stability of biologically active compounds requires an accurate determination of their structure. We have found that 5-aryl-3-(2-aminoethyl)-1,2,4-oxadiazoles are generally unstable in the presence of acids and bases and are rearranged into the salts of spiropyrazolinium compounds. Hence, there is a significant probability that it is the rearranged products that should be attributed to biological activity and not the primarily screened 5-aryl-3-(2-aminoethyl)-1,2,4-oxadiazoles. A series of the 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium (spiropyrazoline) benzoates and chloride was synthesized by Boulton–Katritzky rearrangement of 5-substituted phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles and characterized using FT-IR and NMR spectroscopy and X-ray diffraction. Spiropyrazolylammonium chloride demonstrates in vitro antitubercular activity on DS (drug-sensitive) and MDR (multidrug-resistant) of MTB (M. tuberculosis) strains (1 and 2 µg/mL, accordingly) equal to the activity of the basic antitubercular drug rifampicin; spiropyrazoline benzoates exhibit an average antitubercular activity of 10–100 μg/mL on MTB strains. Molecular docking studies revealed a series of M. tuberculosis receptors with the energies of ligand–receptor complexes (−35.8–−42.8 kcal/mol) close to the value of intermolecular pairwise interactions of the same cation in the crystal of spiropyrazolylammonium chloride (−35.3 kcal/mol). However, only in complex with transcriptional repressor EthR2, both stereoisomers of the cation realize similar intermolecular interactions.

Nitrobenzenesulfochlorination of β-aminopropioamidoximes leads to a set of products depending on the structure of the initial interacting substances and reaction conditions. Amidoximes, functionalized at the terminal C atom with six-membered N-heterocycles (piperidine, morpholine, thiomorpholine and phenylpiperazine), as a result of the spontaneous intramolecular heterocyclization of the intermediate reaction product of an S_N2 substitution of a hydrogen atom in the oxime group of the amidoxime fragment by a nitrobenzenesulfonyl group, produce spiropyrazolinium ortho- or para-nitrobenzenesulfonates. An exception is ortho-nitrobenzenesulfochlorination of β-(thiomorpholin-1-yl)propioamidoxime, which is regioselective at room temperature, producing two spiropyrazolinium salts (ortho-nitrobezenesulfonate and chloride), and regiospecific at the boiling point of the solvent, when only chloride is formed. The para-Nitrobezenesulfochlorination of β-(benzimidazol-1-yl)propioamidoxime, due to the reduced nucleophilicity of the aromatic β-amine nitrogen atom, is regiospecific at both temperatures, and produces the O-para-nitrobenzenesulfochlorination product. The antidiabetic screening of the new nitrobezenesulfochlorination amidoximes found promising samples with in vitro α-glucosidase activity higher than the reference drug acarbose. ¹H-NMR spectroscopy and X-ray analysis revealed the slow inversion of six-membered heterocycles, and experimentally confirmed the presence of an unfavorable stereoisomer with an axial N–N bond in the pyrazolinium heterocycle.