Novel conjugates of rhodamine B with 2-chloro-, 2-chloro-6-methyl-and 2-chloro-6-methoxyquinoline were synthesized. Their structure and ion-induced switching properties were studied using 1 & Ncy;, COSY, 13 & Scy;, HSQC and HMBC NMR, UV-Vis/fluorescence spectroscopy, X-ray diffraction analysis and DFT quantum chemical calculations. The compounds obtained exist in the spirolactam form, which is characterized by the lack of absorption in the region > 500 nm and the absence of emission properties. However, in the presence of Hg2+ cations, they exhibit a selective and contrasting naked eye effect, as a result of which the colorless acetonitrile solution becomes purple. Simultaneously, the appearance of intense emission at 584-588 nm is observed. These changes are due to the opening of the spirocycle, which was confirmed by an additional 1H NMR experiment. The reverse transformation occurs under the action of CN-anions. The observed ion-controlled off-on-off switching of the fluorescence properties was used to develop the logic circuit. For the first time, using PCM/DFT/M06-2X-D3/ Def2-SVP calculations in acetonitrile and AIM analysis, it was shown that the interaction with mercury(II) cations is a multistage process.

The photochromic behavior of N-acetyl (2) and N-propionyl (3) derivatives of 2-((phenylamino)methylene)benzo[b]thiophen-3(2H)-one was investigated in both the solid state and in solution using IR, 1H, 13C NMR spectroscopy, high-resolution mass spectrometry, UV-Vis/fluorescence spectroscopy, and X-ray diffraction analysis, complemented by DFT quantum chemical calculations. Solid-state irradiation of N-acetyl derivative 2 triggers [2+2] photocycloaddition to yield dimer 4, whereas the N-propionyl analog 3 remains photostable under these conditions. Conversely, in acetonitrile solution, irradiation of both 2 and 3 with light of 436 nm induces a multi-step 1,5-sigmatropic N→O acyl migration, resulting in the formation of O-acetyl 5 and O-propionyl 6 isomers. DFT calculations at the M06-2X/Def2-TZVP level, incorporating the PCM solvation model and AIM analysis, were successfully utilized to rationalize the observed phase-dependent photochemical phenomena.

e15158 Background: The aim of this study was to evaluate the antitumor activity of the alkaloid corynan, which we obtained, in silico and in vitro on H1299 and HT29 tumor cell lines. Methods: Corynan was extracted from the plant material Petasites hybridus using preparative chromatography. Its structure was confirmed by Nuclear Magnetic Resonance (NMR) as (2S,3R,12bS)-2,3-diethyl-12b-methyl-1,2,3,4,6,7,7a,12,12a,12b-decahydroindolo[2,3-a]quinolizine. Molecular docking of corynan with five receptors involved in carcinogenesis — EGFR, PDGFR, MET, MRP2, and NOX4—was performed using AutoDock Vina 4.0. PDB structures were imported into Discovery Studio Visualizer 4.0. AlphaFoldDB structures were already cleaned. These structures were optimized prior to docking using Chimera 1.6.2. The resulting .pdb files were validated using the PROCHECK server and aligned with the original structure. These files were used to prepare the grid in AutoDockTools-1.5.7. H1299 (non-small cell lung cancer) and HT29 (colorectal cancer) cells were cultured under standard conditions in MEM medium. Upon reaching 75-80% confluence, the medium was replaced with one containing corynan (128 µM concentration), and the cells were cultured for 72 hours. Cell viability was determined using a NanoEnTek JuliFl (Korea) counter in the presence of 0.4% trypan blue. The assessment of expression levels after treatment was performed by RT-PCR using a gene panel: CASP9, CASP7, CASP3, TP53, MDM2, BAX, BCL2, PTEN, ATM, MTCH1, CYCS, DIABLO, VDAC1. Results: Corynan demonstrated the highest affinity for the MET protein (-8.6 kcal/mol), followed by PDGFR (-7.2 kcal/mol), EGFR and MRP2 (-6.4 kcal/mol and -6.3 kcal/mol), and NOX4 (-5.9 kcal/mol). Corynan at a concentration of 128 µM and 72-hour exposure caused death in 60% of HT29 cells and 36% of H1299 cells. Under the same conditions, corinane caused a 22-fold increase in CASP9 expression in H1299 cells, and in HT29 cells, a 9.5-fold increase in CASP9 expression and a 12.5-fold increase in CASP7 expression. In HT29 cells, it caused an 82-fold increase in BAX expression and a 64-fold increase in MTCH1 expression. No statistically significant changes were observed in the expression of the other investigated genes. Conclusions: Molecular docking of corynan showed that it could be an effective inhibitor of the MET protein—a key factor in invasion and metastasis. The inhibition of viability in HT29 and H1299 cell lines in vitro and the changes in the expression of caspase genes, BAX , and MTCH1 suggest that corynan possesses antitumor activity and provides a basis for its further study.

New F16 derivatives – (E)-4-(1H-indol-3-ylvinyl)-N-alkylpyridinium salts containing phenyl substituents on the pyridine ring were prepared by the reaction of (E)-4-(1-(1-methyl-1H-indol-3-yl)prop-1-en-2-yl)-2,6-diphenylpyrylium perchlorate with amines. The use of pyrylium salts as starting compounds is an advantage over traditional F16 syntheses, based on the reactions of pre-synthesized pyridines, since it allows the introduction of any aromatic and/or aliphatic substituents into the pyridine ring. The obtained compounds exhibit properties of dual-state emission (DSE). The extremely low fluorescence quantum yields in solution (ϕf ≤ 0.004) significantly limit their practical applications. However, the substantially higher quantum yields observed in the solid state (ϕf = 0.023–0.045) suggest their potential utility for imaging in aggregated or membrane-bound systems. Photoinitiated processes in F16 derivatives, along with the fluorescence of the original E-isomeric forms, include photochromism, which allows them to be considered as fluorescent molecular switches. The optical properties of one of the compounds allow it to be used to assess membrane potential in isolated mitochondria and observe its accumulation in mitochondria of living cells by fluorescent microscopy. A comparison of the penetration of the lipophilic cations, both those obtained in this study and known in the literature, through an artificial lipid bilayer membrane in response to the application of a transmembrane electrical potential is carried out.

e14056 Background: Brain tumors present a genuine challenge for medicine due to their anatomical features, high resistance to existing chemotherapeutic drugs, a strongly immunosuppressive environment, and the presence of the blood-brain barrier. The research and development of new anti-tumor drugs remains an important task. Tropolone derivatives represent a promising class of organic compounds that could serve as new pharmaceutical anti-tumor agents. There is currently a growing interest in tropolone alkaloids, as many of them possess a broad spectrum of pharmacological activity. The aim of the study was to investigate the cytotoxic effect of a new tropolone derivative 2-(1,1-dimethyl-1H-benzo[e]indoline-2-yl)-5,6,7-trichloro-1,3-tropolone (JO-122(2)) on primary glioma cell cultures in an in vitro experiment. Methods: The tumor material for primary cell cultures was obtained from a patient who was diagnosed with grade 4 glioblastoma on the background of anaplastic astrocytoma (Culture 1) and a patient with histologically verified grade 4 giant cell glioblastoma (Culture 2) who were treated at the Department of Neuro-Oncology of the National Medical Research Centre for Oncology of the Ministry of Health of the Russian Federation. Cell cultures were cultured on DMEM medium (Gibco, USA) with the addition of 10% FBS (Hyclone, USA). The cells were planted in a 96-well plate (Eppendorf, Germany) in the amount of 5,000 cells in 100 µl of medium per well and incubated for 24 hours at a temperature of 37 ° C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing JO-122(2) in a series of double dilutions. The maximum amount of JO-122(2) was 24 μmol. The MTT test was performed according to the standard procedure, the exposure time was 24, 48 and 72 hours. The optical density was determined at a wavelength of 540 nm using a tablet reader. The inhibition index (IC50) was defined as the percentage of surviving cells after exposure to JO-122(2) from the control. Results: The results of the in vitro cytotoxic effect study showed that the IC50 for Culture 1 after incubation with the addition of JO-122(2) for 24 hours was 5.3668 μmol, 48 hours - 3.9358 μmol, 72 hours - 1.5418 μmol. For Culture 2, the IC50 after incubation for 24 hours was 2.9146 μmol, 48 hours - 2.1581 μmol, 72 hours - 1.1187 μmol. Conclusions: Our results indicate that JO-122(2) has a pronounced cytotoxic effect on primary glioma cell cultures. It is noted that an increase in the duration of incubation contributes to a decrease in cell viability.

e19114 Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that accounts for 25% of all adult cases of T-ALL. Currently, the frequency of disease recurrence and resistance to therapy remains quite high, so there is an urgent need to improve therapy by testing new compounds that may potentially have antitumor activity. Promising compounds include berberine, whose high antitumor activity we previously confirmed on glioblastomas, and its derivatives. The aim of the study was to evaluate the cytotoxic effect of berberine derivatives on Jurkat cell culture in an in vitro experiment. Methods: Jurkat cell culture cells were cultured in a complete RPMI1640 nutrient medium without phenolic red (Gibco, USA) with the addition of 10% FBS (Hyclone, USA), 1% glutamine (Biolot, Russia). A total of 11 compounds were tested: berberine and its derivatives ZbRNN, Rub, NAPh, Rub HCl, 12NO2, EPOX, Mag-2, Mag-1, AkR(1) Fuz, 21A. Dose-response curves were constructed for each compound, measuring the level of metabolically active cells by colorimetric method using tetrazolium salt XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide). The exposure time was 72 hours. Viability was determined as the ratio of the number of living cells in the experimental wells to the control wells, expressed as a percentage. Based on the data obtained, dose-response curves were constructed and IC50 values were determined using the dcr package of the R programming language. Results: Compounds MAG-1, MAG-2, 21A, ZbRNN, Rub, 12NO2, EPOX, and NAPh demonstrated high activity (IC50 below 1000 nmol/L) against the Jurkat cell line. The IC50 value for the studied substances was: 236.4±33.5 nmol/L, 31.8±9.1 nmol/L, 126.3±27.2 nmol/L, 103.8±13.3 nmol/L, 136.4±18.7 nmol/L, 308.4±39.3 nmol/L, 455.7±54.1 nmol/L and 789.5±26.6 nmol/l, respectively (p<0.05). For compounds Rub HCl and AkR(1) Fuz, the IC50 value exceeded 1000 nmol/l and amounted to 1756.2±99.1 nmol/l and 1435.7±112.8 nmol/L (p<0.05). For berberine, the IC50 value was 447.6±46.1 nmol/L. Conclusions: The results obtained indicate the pronounced cytostatic properties of a number of berberine derivatives, of particular interest are compounds that are close to and superior to berberine in cytostatic properties.

New photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophen-3(2H)-ones containing a terpyridine receptor have been synthesized. They absorb in the visible region of the spectrum at 423-426 nm and exhibit emission at 463-468 nm. Their irradiation in acetonitrile with light of 436 nm leads to a multi-stage rearrangement, including Z/E isomerization about the C--C bond, N -> O migration of the acyl group and the formation of non-emissive O-acylated E-isomers, which were isolated preparatively. Their structure was established unambiguously by IR, 1H, 13C NMR spectroscopy and HR mass spectrometry. The reverse thermal reaction with O -> N migration of the acyl group is catalyzed by acid catalysts. N-Acylated compounds in acetonitrile selectively form non-fluorescent complexes with Fe2+ cations, which is accompanied by the naked-eye effect with changing the color from yellow to maroon. A successful selective interaction with AcO- led to the restoration of the initial absorption and emission properties. Density functional theory (DFT) calculations at the M06-2X/def2TZVP level with the PCM solvation method were used to explain the observed photoisomerizations and ionochromic transformations. The obtained compounds represent multifunctional on-off-on molecular switches of optical and fluorescent properties upon sequential exposure to light and H+ or sequential addition of Fe2+ and AcO- ions. A combinatorial logic gate was designed based on the basis of these switching properties.

The potential energy surfaces (PESs) for a number of reactions between substituted acetylenes and substituted 2H-thiopyran-2-thiones, as well as their isoelectronic analogues were studied by PCM/DFT/B3LYP/6-311++G(d,p) quantum chemical calculations. Theoretical studies have revealed the similarity of the PESs, which differ from each other only in their energetic characteristics. Similar reaction channels on these surfaces lead to different products through six similar minimum-energy pathways (MEPs). In the case of an excess of acetylene, the formation of 4-thiophene-substituted thiopyran derivatives is energetically preferred.

The efficiency of combining experimental methods and quantum chemical calculations (DFT and ab initio) for optimizing conditions and predicting mechanisms for the interaction of acyclic and cyclic derivatives of indole‐2,3‐quinodimethane with heterodienophiles is demonstrated. For the reactions of acyclic derivatives of indole‐2,3‐quinodimethane with nitriles and carbon disulfide, indoles, [b]‐fused with nitrogen‐ and sulfur‐containing six‐membered rings, were synthesized. Quantum chemistry methods have shown that the addition of nitriles and carbon disulfide to indole‐2,3‐quinodimethane derivatives occurs through cyclic transition states involving a lithium atom. Calculations have substantiated the choice of a non‐polar aprotic solvent to increase the yield of γ‐carbolines. It has been shown for the first time that the replacement of the oxygen atom in cyclic derivatives of quinodimethane—pyrano[4,3‐b]indol‐3(5H)‐ones by sulfur leads to a complete change in the direction and mechanism of their reaction with dimethyl acetylenedicarboxylate: instead of the usual [4+2] cycloaddition in the case of an oxygen‐containing substrate, cascade processes are realized, including alkyne‐thiocarbonyl metathesis and [3+2] cycloaddition.

Bifunctional hybrids of a new type containing photochromic indolyl(thienyl) diarylethenes with a pyrroldione bridge directly linked by a dimethylene spacer to an ionochromic rhodamine moiety were synthesized. The synthesized hybrids in toluene exhibit absorption at 450-455 nm and fluorescence at 560 nm. Irradiation with UV light leads to the formation of ring-closed non-fluorescent diarylethene isomeric fragments. Under visible light (or gradually in the dark conditions), reverse isomerization to the initial forms occurs. The spectral and kinetic characteristics of the processes have been studied. In the presence of H+ cation, a striking naked eye effect is observed due to the opening of the rhodamine-spirolactam ring and appearance of a characteristic pink-crimson coloration at 561 nm along with intense long-wavelength emission at 586 nm. This process is completely reversible upon exposure to triethylamine. The mechanism of this transformation was confirmed by additional 1H and 13C NMR experiments. The M06-2X/Def2-TZVP method and AIM analysis were successfully used to explain observed light-induced isomerizations as well as proton-induced transformations. Thus, revers-ible switching of the fluorescent properties of hybrid molecules can be operated by light irradiation and proton.

The heterocyclic core of imidazo[1,2-a]pyrimidine was formed in satisfactory yields as a result of the interaction of the readily available 2-aminoimidazole with N-substituted maleimides or N-arylitaconimides. The mechanism of the studied processes was postulated basing on experimental data, HPLC–MS analysis of reaction mixtures, and quantum chemical calculations. Molecular docking results of the obtained imidazo[1,2-a]pyrimidines, when compared with voriconazole, a drug already in clinical use, suggest that they may possess antifungal activity against Candida albicans.

Purpose of the study. To evaluate the cellular, genomic (gene copy number) and transcriptomic (gene expression) effects of P.hybridus (L.) secondary metabolites when they affect the HeLa cell line.Materials and methods. The isolation of secondary metabolites from plant material and its identification were carried out by preparative chromatography. The composition was determined using mass spectrometric analysis, and the final verification of structural formulas was carried out by nuclear magnetic resonance at the Department of Natural Compounds, the Faculty of Chemistry of the Southern Federal University. The subsequent phase of the study was conducted using both cultural and molecular methods. HeLa cells were cultivated under standard conditions in a MEM medium. Once the confluence level was reached 75–80 %, the nutrient medium was replaced with the introduction of the studied compounds (at a concentration of 4 micrograms/ml) and cultivated for 72 hours. Cell mortality was determined using a NanoEnTek JuliFl counter (Korea) in the presence of 0.4 % trypan blue. The assessment of apoptosis following secondary metabolite exposure was conducted on a BD FACSCanto II flow cytometer using the FITC Annexin V Apoptosis Detection Kit I. The level of replication and expression of the genes responsible for apoptosis was assessed by digital droplet PCR (ddPCR).Results. The following compounds were isolated and verified, and were assigned the following sequence numbers to facilitate their use in the experiment: No. 2 – 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one, No. 3 – 5-(hydroxymethyl) furan-2-carbaldehyde, No. 5.3 – 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde, P. hybridus (L.) At the stage of cell death assessment, it was found that the greatest effect was achieved in the compound under ordinal No. 2. However, the evaluation of the copy number and expression of the CASP8, CASP9, CASP3, BAX, BCL2, TP53, MDM2, CDKN1B, CDK1, CCND1, CCND3, and RB1 genes by DD-PCR revealed the presence of apoptosis initiation in tumor cells at the molecular level under the action of compounds No. 2 and No. 5.3 obtained from P. hybridus (L.).Conclusion. The outcomes were multifeatured. Only compound 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one exhibited a pronounced cytostatic effect out of all compounds utilized in the experiment. Concurrently, the compound 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde was found to induce an increase in the expression of the CASP3, CASP8, TP53, and BAX genes.

While it is well established that a mere 2% of human DNA nucleotides are involved in protein coding, the remainder of the DNA plays a vital role in the preservation of normal cellular genetic function. A significant proportion of tandem repeats (TRs) are present in non-coding DNA. TRs - specific sequences of nucleotides that entail numerous repetitions of a given fragment. In this study, we employed our novel algorithm grounded in finite automata theory, which we refer to as Dafna, to investigate for the first time the likelihood of these nucleotide sequences forming non-canonical DNA structures (NS). Such structures include G-quadruplexes, i-motifs, hairpins, and triplexes. The tandem repeats under consideration in our research encompassed sequences containing 1 to 6 nucleotides per repeated fragment. For comparison, we employed a set of randomly generated sequences of the same length (60 nucleotides) as a benchmark. The outcomes of our research exposed a disparity between the potential for NS formation in random sequences and tandem repeats. Our findings affirm that the propensity of DNA and RNA to form NS is closely tied to various genetic disorders, including Huntington's disease, Fragile X syndrome, and Friedreich's ataxia. In the concluding discussion, we present a proposal for a new therapeutic mechanism to address these diseases. This novel approach revolves around the ability of specific nucleic acid fragments to form multiple types of NS.

Introdution. Cancer is the second leading cause of death in Russia and the world after cardiovascular diseases. Chemotherapy remains the main line of treatment, but tumor cells can become resistant to drugs. Researchers are working on new effective drugs, including secondary metabolites of plants that have antitumor effects through various mechanisms. The aim of this study was to investigate the cytotoxic properties of three compounds: alkaloid P1, terpenoid P2, and flavonoid V1 against pancreatic cancer cell line AsPC-1 and non-small cell lung cancer H1299. Material and methods. Secondary metabolites of Petasites hybrydicus (L.) G. Gaertn., B.Mey. & Scherb. and Viscum album L. were extracted using tetrachloroethylene. For identification of the isolated compounds, high-performance liquid chromatography with mass detection and nuclear magnetic resonance method were used. Non-small cell lung cancer cell line H1299 and pancreatic cancer AsPC-1 were grown in RPMI1640 medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) and 1% glutamine (Biolot, Russia) under standard conditions. Cell sensitivity to the studied compounds was determined by MTT test. Results. All three compounds demonstrated antitumor activity against the studied cell lines. Compound V1 increased signs of mesenchymal cells morphology and apoptosis, with IC50 values of 234.24±21.56 μM (AsPC-1) and 565.62±84.31 μM (H1299). Compound P1 promoted multinucleated cell formation in H1299 culture. Half-inhibitory doses for P1 were 652.54±56.12 μM (AsPC-1) and 157.85±48.62 μM (H1299). Compound P2 induces cell apoptosis and necrosis and probably affects membrane rigidity. The IC50 values for P2 were 802.34±121.02 μM (AsPC-1) and 415.71±75.05 μM (H1299). Conclusions. These compounds can be considered promising antitumor agents for lung cancer and pancreatic cancer.

The chemistry of heterocyclic compounds has traditionally been and remains a bright area of chemical science in Russia. This is due to the fact that many heterocycles find the widest application. These compounds are the key structural fragments of most drugs, plant protection agents. Many natural compounds are also derivatives of heterocycles. At present, more than half of the hundreds of millions of known chemical compounds are heterocycles. This collective review is devoted to the achievements of Russian chemists in this field over the last 15–20 years. The review presents the achievements of leading heterocyclists representing both RAS institutes and university science. It is worth noting the wide scope of the review, both in terms of the geography of author teams, covering the whole of our large country, and in terms of the diversity of research areas. Practically all major types of heterocycles are represented in the review. The special attention is focused on the practical applications of heterocycles in the design of new drugs and biologically active compounds, high-energy molecules, materials for organic electronics and photovoltaics, new ligands for coordination chemistry, and many other rapidly developing areas. These practical advances would not be possible without the development of new fundamental transformations in heterocyclic chemistry. Bibliography — 2237 references.

The possibility of synthesizing 12-(aryldiazo)berberrubines was demonstrated experimentally and by quantum-chemical calculations based on the Density Functional Theory in the B3LYP/6-31G(d,p) basis set. In weakly alkaline media, berberrubine can be substituted at position 12 by azo coupling reactions with aryldiazonium salts. This process proceeds in steps: first, berberrubine transforms into the zwitterionic form of 9-oxoberberine, which then enters as a nucleophile into an azo coupling reaction with aryldiazonium salts to form a single product with the trans configuration of the fragments relative to the N=N double bond. The resulting 12-(aryldiazo)berberrubines may find use as antibiotic agents, as shown on the multidrug-resistant culture Acinetobacter lwoffii .

Reaction of thiopyrano[4,3-b]indole-3(5H)-thiones and dimethyl acetylenedicarboxylate (DMAD) proceeds via two competing cascade pathways. Initially, both the pathways begin from thiocarbonyl sulfur and acetylene carbon atoms interaction. Then two parallel processes take place: an alkyne-thiocarbonyl metathesis and a (3 + 2) cycloaddition. In the next stages, in both cases, thiophene ring formation and thiopyran ring opening proceed. Finally, (4 + 2) cycloaddition reactions of intermediate thioketones and a second equivalent of DMAD leads to the resulting thiopyrano[4,3-b]indole derivatives bearing thienyl substituent. The kinetic and thermodynamic characteristics of both pathways were compared on the basis of DFT and ab initio 6-311++G(d,p) quantum chemical calculations.

We developed a microfluidic synthesis with UV-Vis diagnostics using a 3D printed chip for 8,13-disubstituted berberines. This system yielded up to 30% higher product yields with high antioxidant activity compared to traditional batch synthesis.

Purpose of the study. To isolate and verify pure fractions of secondary plant metabolites contained in B. vulgaris (L.) and P. hibridus (L.), as well as to conduct a model experiment and molecular genetic study to evaluate their cytotoxic effect in vitro on the HeLa cell line.Materials and methods. The isolation and verification of all compounds used in the experiment were carried out using column chromatography and nuclear magnetic resonance methods at the Department of Natural Compounds, Faculty of Chemistry, Southern Federal University. Subsequently, an experiment was conducted using cultural and molecular methods on the HeLa cell line in three repetitions for each test compound; after incubation with them, the numbers of dead cells were counted on the automated NanoEnTek JuliFl counter, and the numbers of cells in apoptosis were measured by flow cytometry on the BD analyzer FACS Canto II. The level of copy number variation and expression of genes responsible for apoptosis were assessed by real-time PCR (RT-PCR). In total, three substances were studied, with two concentrations (4 and 12 μg/ml) and two exposures (24 and 72 hours) for each of them.Results. In the first stage of the study, we isolated and verified the berberine alkaloid extracted from the roots of B. vulgaris (L.), as well as 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one and 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde from P. hibridus (L.). The subsequent stage of the study demonstrated the maximal cellular death under the action of berberine at a 72-hour exposure. However, the RT-PCR assessment of the copy number variation and expression of the CASP8, CASP9, CASP3, BAX, BCL2, TP53 and MDM2 genes revealed the presence of apoptosis initiation in tumor cells at the molecular level under the action of all the studied compounds: both berberine and furan and azulene derivatives derived from P. hibridus (L.).Conclusion. All compounds used in the experiment exhibited a cytotoxic effect on the HeLa cell line. Berberine alkaloid showed the most pronounced cytotoxic effect on the HeLa line as recorded by all methods used in the study. Terpenoids 4-dihydroxy-2,5-dimethylfuran-3(2H)-one and 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde, when exposed to the HeLa line, caused an increase in the copy number variation and expression of the CASP9, CASP3 loci, which are among the main activators of apoptosis. They also influenced the expression of TP53 and MDM2 loci.