This study explores the phytochemical composition and antimicrobial potential of Palustriella commutata, Philonotis calcarea, Cinclidotus riparius, Rhynchostegium riparioides, Plagiomnium ellipticum, and Porella platyphylla, with a focus on bryophyte species phenolic constituents and biological activities. HPLC analysis identified seven phenolic acids (4-hydroxybenzoic acid, 2,5-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, caffeic acid, vanillic acid, syringic acid, and p-coumaric acid) across all species in varying concentrations. In in vitro antimicrobial tests, the bryophyte extracts used showed significant activity against Pseudomonas aeruginosa (ATCC 9027), while exhibiting relatively lower inhibition against Staphylococcus aureus (ATCC 25923). The study showed that all species extracts exhibited comparable activity to erythromycin against P. aeruginosa, while Cinclidotus riparius and Plagiomnium ellipticum extracts showed no activity against S. aureus, and the remaining species exhibited lower activity compared to erythromycin. Molecular docking studies demonstrated strong binding affinities of these phenolics to the active site of the target macromolecule (PDB ID: 3FRQ), suggesting meaningful interactions with residues such as ARG122 and ASN123, similar to erythromycin binding patterns. The findings indicate that bryophyte-derived phenolic compounds possess significant antimicrobial potential and may serve as promising candidates for the development of novel bioactive agents. This study provides a broad framework for the insufficiently researched antimicrobial potential of bryophytes by establishing direct links between species-specific phenolic fingerprints, experimentally observed antibacterial activities, and predicted receptor-level interactions. Further complementary biological studies are needed to confirm and expand upon these results.

This study aimed to demonstrate in vitro and in silico antimicrobial efficacy of the fixed oil derived from the seeds of Sanguisorba minor Scop., a plant traditionally utilized for wound healing, burn treatment, and hemorrhage control. As a result of GC–MS analysis, 14 distinct saturated and unsaturated fatty acids, predominantly linoleic acid (11, 43.25%), α‐linoleic acid (12, 25.33%), and oleic acid (10, 20.73%) were determined. The DPPH• and ABTS+ radical scavenging effects of the oil were determined to be of low‐middle activity. As a result of antibacterial and antifungal activities, MIC values against tested Gram‐positive and Gram‐negative species ranged between 1.406 and 11.25 µL/mL. While the MBC values of plant fixed oil for bacterial species ranged between 22.5 and 45 µL/mL, this value varied between 5.625 and 11.25 µL/mL for Candida species. Molecular docking studies revealed that the antifungal and antimicrobial activities of our ligands are expected to occur at micromolar levels. In particular, the antimicrobial activity of the fixed oil was demonstrated by the higher docking scores and inhibitory effects at lower concentrations of oleic acid (10), linoleic acid (11), and α‐linolenic acid (12), which specifically played a role in this process.

This study examined the effects of dietary ellagic acid (EA) on growth performance, survival, immune responses, and oxidative status of common carp (Cyprinus carpio) exposed to high stocking density (HSD). A 2 × 3 factorial design was used, with two stocking densities (25 and 100 kg/m3) and three EA levels (0, 50, and 100 mg/kg diet). HSD significantly reduced growth performance, as indicated by lower weight gain and specific growth rate (SGR), increased feed conversion ratio (FCR), and decreased survival (p < 0.05). It also suppressed immune responses, including white blood cell count (WBC), nitroblue tetrazolium activity (NBT), phagocytic activity (PA), lysozyme activity (LYZ), and bactericidal activity (BA). Furthermore, HSD increased malondialdehyde High stocking density caused (MDA) levels and decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in liver, head kidney, and spleen tissues (p < 0.05). Fish were challenged by intraperitoneal injection of Aeromonas salmonicida subsp. achromogenes. Dietary EA supplementation significantly improved survival under both stocking densities, with the highest survival observed in fish receiving 100 mg/kg EA. Kaplan-Meier survival analysis and log-rank tests confirmed significant differences among treatment groups (p < 0.05). Pairwise comparisons further demonstrated that EA, particularly at 100 mg/kg, enhanced survival under high-density conditions. EA supplementation also improved growth performance, antioxidant status, and immune responses in a dose-dependent manner. Polynomial contrast analysis revealed significant linear trends: increasing EA levels enhanced weight gain, antioxidant enzyme activities, and immune parameters, while reducing MDA levels (p < 0.05). Significant SD × EA interactions indicated that EA alleviated the adverse effects of crowding stress. In silico analyses showed higher binding affinity of EA toward SOD, CAT, and GSH-Px. Overall, dietary EA effectively mitigated density-induced oxidative stress and immunosuppression, supporting its potential as a functional feed additive in intensive aquaculture.

This study aims to perform molecular docking analyses of a newly synthesized candidate compound and to investigate its therapeutic efficacy in vivo at an appropriate dose in a female rat model with induced breast cancer. To this end, the Cys-PA-Kum-OH compound (coumarin-containing cysteine amino acid conjugate) was synthesized for the first time within the scope of this study. The rats were divided into seven groups, each consisting of 12 animals. Following, molecular biological and histopathological analyses were conducted. As a result, MDA (malondialdehyde) levels decreased in the treatment groups, whereas CAT (catalase) and GSH (glutathione) levels significantly increased. Moreover, the expression levels of COX-2 (cyclooxygenase), HER2 (Human Epidermal Growth Factor Receptor), and TNF-α (Tumor necrosis factor) were downregulated in the treated groups, while p53 (Tumor protein) expression was upregulated. Histopathological examinations performed to assess tumor size and histological type revealed that invasive tumors were more prevalent in the damage (control) groups. In contrast, reduced tumor incidence and a significant decrease in tumor size were observed in the groups treated with the amino acid conjugate (AC) and tamoxifen (TAM). Based on these findings, the Cys-PA-Kum-OH conjugate exhibits protective properties against breast cancer, positioning it as a promising candidate for further investigation.

Lead (Pb) is a widespread environmental pollutant that induces systemic toxicity in aquatic organisms primarily through oxidative stress, hematological disruption, and immune dysfunction. This study investigated the protective effects of ellagic acid (EA) against Pb-induced toxicity in common carp (Cyprinus carpio) using a multi-biomarker approach and molecular docking. Fish were assigned to six experimental groups: control, EA-treated, Pb-I, Pb-I + EA, Pb-II, and Pb-II + EA. Fish in the Pb-I and Pb-II groups were exposed to 2.5 and 5 mg/L Pb, respectively, while EA was administered via diet at 100 mg/kg for 14 days. At the end of the exposure period, hematological indices, innate immune parameters, and oxidative stress biomarkers were assessed in blood, liver, kidney, and gill tissues. Pb exposure caused marked hematological impairment, suppressed immune responses, increased malondialdehyde levels, and disrupted antioxidant defense by reducing SOD, CAT, GSH-Px, and GSH levels while increasing GST activity. In contrast, dietary EA supplementation significantly mitigated Pb-induced alterations, improved hematological and immunological responses, reduced lipid peroxidation, restored antioxidant capacity, and normalized GST activity to control levels. Molecular docking analyses further showed that EA interacts with hemoglobin and immunoglobulin M, supporting its potential role in preserving oxygen transport and immune functions under Pb-induced stress. Overall, the findings demonstrate that Pb-induced toxicity involves coordinated disruption of redox homeostasis and immune function, whereas EA exerts a multi-target protective effect through biochemical and molecular mechanisms. This study provides mechanistic insight into chemical-biological interactions and supports the potential application of natural bioactive compounds in mitigating heavy metal-induced toxicity.

Background/Objectives: Predicting the bioactivity of HIV-related compounds is essential for early-stage drug discovery. However, most existing machine learning (ML) studies emphasize predictive performance while overlooking the predicted pharmacokinetic and drug-likeness properties of prioritized compounds. This study presents a comparative framework integrating classical ML, deep learning, graph-based models, and complementary ADME-based pharmacokinetic assessment. Methods: Twelve predictive models were evaluated using stratified five-fold cross-validation on the MoleculeNet HIV dataset under a unified experimental protocol. Model performance was assessed using multiple classification metrics together with statistical analysis. The highest-ranked compounds from the independent test set were further characterized using predicted ADME and drug-likeness properties. A representative compound (GDL1), prioritized by the GDL model, was subsequently evaluated by molecular docking against HIV-1 protease, HIV-1 integrase, and HIV-1 reverse transcriptase. Results: The graph-based GDL model achieved the highest ROC–AUC (0.956±0.015), followed by GRU (0.930±0.017) and RF (0.927±0.023). Statistical analysis indicated overall differences among model performances (Friedman test, p<0.001). However, Holm-corrected pairwise comparisons did not demonstrate statistically significant differences between the highest-performing models. Comparative ADME analysis showed that high predictive performance did not necessarily correspond to favorable predicted pharmacokinetic properties. Molecular docking suggested potential predicted binding interactions of the prioritized GDL1 compound with all three HIV-1 targets, with the most favorable predicted binding affinity observed for HIV-1 reverse transcriptase. Conclusions: The proposed framework enables a comprehensive comparison of diverse molecular learning approaches by integrating predictive performance with complementary predicted ADME, drug-likeness, and molecular docking analyses.

Polyphenol oxidase (PPO) has been the subject of many inhibition studies due to its presence in many species, causing enzymatic browning in fruits and vegetables, and its pigmentation role in mammalian species. In the present study, the inhibitory properties of twelve 1-alkyl-1H-benzimidazolium sulfonates and two 1-alkyl-1H-benzimidazolium iodides on PPO activity have been investigated. The PPO enzyme was purified from banana using Sepharose 4B-tyrosine-p-aminobenzoic acid affinity gel chromatography. The effects of 14 different synthesized benzimidazole derivatives on the PPO enzyme were investigated, and they were found to significantly inhibit the enzyme in question. When ADME predictions were examined, it was seen that all compounds that include methylbenzenesulfonate structure showed good pharmacokinetic properties; only compounds 3a and 3b, which contain iodide, violated the Ghose rules. These compounds, which were effective at low concentrations, may serve as promising lead molecules for the development of PPO inhibitors with potential applications in food preservation, cosmetic formulations, and pharmaceutical research, pending further in vivo and formulation-based studies.

Since plant essential oil contains medicinally valuable compounds, its usability as a pharmacotherapeutic agent has been the focus of attention within the century's needs. The lack of sufficient studies on the medical and pharmacological evaluation of Fibigia clypeata (L.) Medik has made this plant the target of our study. This study analyzes the phytochemical composition and biological activity of F. clypeata essential oil. As a result, dimethyl disulfide and dimethyl trisulfide were found to be the main compounds of the plant essential oil, with rates of 73.13% and 19.87%, respectively. The antifungal property of plant essential oil is more effective than its antibacterial property, with MIC values ranging between 0.039 and 0.312 μL/mL for fungal species and up to 3.750 μL/mL for bacterial species. The enzyme inhibition profiles were investigated towards two enzymes, namely, anticholinesterase and α-glucosidase, targeted for anti-diabetic studies. Anticholinesterase activity was proved with the IC50 values of 17.31 and 4.78 μg/mL for Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) enzymes, respectively. DPPH and CUPRAC activities were the most promising antioxidant studies, with values of 1.54 and 3.72 μg/mL. It was observed that α-Terpineol made a hydrogen bond with ASN80, and 1-(2,6,6-Trimethyl-1,3-cyclohexadien-1-yl)ethanol made a hydrogen bond with SER82. Although molecular dock scores were better for antifungal activity, it was determined that no interactions, such as hydrogen bonding or pi interaction, were observed. This preliminary study showed that F. clypeata essential oil is a natural source with promising in vitro antimicrobial, antioxidant, and anticholinesterase activities that warrants further investigation, including safety assessments, due to the high concentration of sulfur-containing compounds. Molecular docking and ADME prediction results showed that α-Terpineol and 1-(2,6,6-Trimethyl-1,3-cyclohexadien-1-yl)ethanol were more prone to antimicrobial activity.

In this study, we have aimed to determine the in vitro and in silico effects of 23 frequently used dermatologic drugs on human carbonic anhydrase I (hCA I) and II (hCA II). The inhibitory effects of the drugs on hCA I and hCA II were determined by esterase methods. The most potent inhibitors were isotretinoin for hCA I (Ki= 5.75 µM) and valaciclovir for hCA II (Ki= 5.74 µM). Ketotifen (Ki= 6.98 µM), pantoprazole (Ki= 7.16 µM) and acyclovir (Ki= 7.31 µM) were also potent inhibitors for hCA I. Isotretinoin (Ki= 6.54 µM), brivudine (Ki= 7.44 µM) and fluconazole (Ki= 7.91 µM) were also potent inhibitors for hCA II. Terbinafine hydrochloride was a weak CA inhibitor for both of these isoenzymes (Ki= 20.58 µM for hCA I and 20.32 µM for hCA I). Therefore, the drug, having a weak CA inhibitory activity, may be preferred primarily in patients with a skin disease compared to the other drugs due to important physiological functions of CAs. Molecular docking studies have shown that acitretin and isotretinoin, in particular, will inhibit hCA I at lower concentrations and have higher docking scores. For hCA II, it was shown that Isotretinoin and Ketotifen would inhibit at lower concentrations and have higher placement scores.

Since cancer is one of the leading causes of human death, recent research has largely focused on developing multi-target drug designs. In this study, we designed and synthesized a series of piperazine-oxadiazole derivatives as aromatase inhibitors for the treatment of cancer. Their structures were confirmed by 1 H NMR, 13C C NMR, HRMS and FTIR spectroscopic methods. Cytotoxicity (MTT) was performed to determine the anticancer activity of the compounds as aromatase inhibitors against breast (MCF7), fibroblast (NIH3T3) and lung (A549) cell lines. Letrazol was used as the reference agent, compound 4b exhibited a significant effect among other derivatives with a value of IC50=2.103 +/- 0.088 50 =2.103 +/- 0.088 mu M against the MCF7 cell line. Docking study showed that 4b was one of the compounds with the best pose on the aromatase. The docking study showed that 4e was one of the compounds that gave the best pose on EGFR and topoisomerase. When the aromatase, EGFR and topoisomerase docking results were compared, it was concluded that our synthesized compounds may be more effective on the Aromatase macromolecule. From the obtained evaluations of the designed batches, compound 4b appeared to be a promising agent as an aromatase inhibitor for further research and evaluation studies in the future.

The EGFR inhibition treatment option, discovered due to in-depth research into the existence of a wide variety of cancer diseases and their treatment, has opened a new path in drug design and development. This study designed and synthesized 10 new cyclic secondary amine derivatives containing dithiocarbamate as EGFR inhibitors for cancer treatment. Moreover, it is derivatized with benzoxazinone or benzothiazonone rings. The structures of the newly synthesized compounds were elucidated by 1H NMR, 13C NMR, and HRMS spectroscopic methods. MTT analyses were performed to determine the antiproliferative activity of all synthesized compounds (2a-j). All synthesized compounds and Doxorubicin used as a reference drug, were tested against A549 and NIH3T3 cell lines. Compounds 2f and 2g, which gave the best results against the cell lines, were compared with erlotinib, an EGFR inhibitor, for EGFR tyrosine kinase inhibition. The IC50 value of the compound 2f with the best result was found to be 0.079 +/- 0.002 mu M, while the IC50 value of the reference drug Erlotinib was found to be 0.003 +/- 0.001 mu M. As a result of molecular docking studies, it was observed that compounds 2f and 2g had the best poses on the active site of EGFR (PDB ID: 4HJO) and interacted with amino acids important for activity. After in vitro and in silico studies evaluations of the designed and synthesized compounds, it was revealed that compounds 2f and 2g were promising compounds in future advanced EGFR inhibition research studies. Among the benzothiazinone and benzoxazinone derivatives carrying the same groups, benzothiazinone derivatives were found to have higher EGFR inhibitory effects.

The discovery of novel therapeutic molecules against the Human Immunodeficiency Virus (HIV) remains a critical research priority due to the persistent global impact of the disease. Traditional drug discovery processes are often time-consuming, costly, and limited in predictive capacity at early stages. In this study, we propose a three-stage AI-supported framework that integrates deep learning and molecular docking to accelerate candidate identification. First, a customized Autoencoder-Long Short-Term Memory (LSTM) model was employed to generate novel molecular structures consistent with key pharmacokinetic rules. Second, a Geometric Deep Learning (GDL) model was designed to evaluate interactions with major HIV-1 targets, including integrase, protease, and reverse transcriptase. Finally, In silico docking simulations assessed binding affinities and inhibition constants. The framework generated molecules that not only complied with pharmacokinetic and drug-likeness criteria (e.g., QED, ADME, SAScore) but also demonstrated favorable binding properties, particularly towards HIV-1 reverse transcriptase. These findings highlight the potential of the proposed approach to complement early-stage drug discovery and to contribute to the design of promising lead compounds for further experimental validation.

Serotonin (5-HT) and its receptors are involved in various neuropsychiatric disorders, and altered serotoninergic neurotransmission and interactions between the 5-HT and dopamine (DA) systems contribute to the pathophysiology of psychotic disorders. Interactions with 5-HT receptors may contribute to the elucidation of the properties of modern antipsychotic drugs, whose long-term effects on 5-HT receptors have not yet been adequately evaluated. Many people in society show at least one of the symptoms of psychotic disorder, and the mortality rate is twice as high as that of a healthy person. In this study, we revealed the molecular docking results of some drug molecules defined as atypical antipsychotics on 5-HT1A, 5-HT2A, and 5-HT2C. We aimed to contribute to the development of new compounds that may be useful in the treatment of psychotic disorders by trying to demonstrate the relationship between their computational inhibitory activities and their structural properties. Docking study showed that Lurasidone (e) was one drug molecule with the best docking scores on the receptors. Also, it showed that Risperidone (h), Paliperidone (f), and Brexpiprazole (b) were one drug molecules with the best pose on the receptors. Considering ADME predictions, all drug molecules (a-j) had good pharmacokinetic profiles, but Lurasidone was found to have some disadvantages. It seems that the use of Paliperidone and Risperidone may be more valuable, especially in the treatment of psychotic patients such as schizophrenia.

Small molecule PARP inhibitors, such as olaparib, have been developed as part of personalized cancer treatment strategies. This study investigated the synthetic lethality between the PARP enzyme in breast cancer cell lines. The anti-cancer effects of combining the PARP inhibitor olaparib with the small molecule PLK1 inhibitor BI-2536 on MCF-7 and MDA-MB-231 breast cancer cells were assessed through in vitro cell viability (MTT) and clonogenic cytotoxicity analyses. The impact of olaparib and BI-2536 treatment on cell cycle and DNA damage response proteins was analyzed using Western blotting. BRCA2 expression was silenced using RNA interference technology, and the manipulation of BRCA2 gene expression in MCF-7 breast cancer cells was confirmed by Western blotting. Cell viability and colony survival were evaluated in BRCA2-effective and BRCA2-defective MCF-7 cells. Additionally, molecular docking analyses provided insights into the functioning of protein signaling pathways. Our results indicate that the combined treatment with olaparib and BI-2536 significantly reduces the viability of MCF-7 and MDA-MB-231 breast cancer cells and inhibits their colony formation ability. This combination therapy demonstrated a synergistic cytotoxic effect, causing potentiated DNA damage induction in these breast cancer cells compared to individual treatments. The increased expression of PLK1, p53, p21, γH2AX, Nrf-2, cyclin E, A, and B1, along with the decreased expression of HER-2, NF-κB, and cyclin D1 in breast cancer cells, suggests that PLK1 inhibition can enhance the efficacy of PARP inhibitors.

This study was designed to synthesize hybrid molecules starting from 2,6-diisopropyl aniline (1), which is similar to Propofol (2,6-diisopropyl phenol), by increasing its biological activity with other heterocycles and to determine the anesthetic activity of the obtained compounds. For this purpose, commercially available 2,6-diisopropylaniline (1) was used as a starting compound. Then, ester (2), hydrazide (3), carbothioamide (5, 6) and Schiff bases derivatives (4 a-f) were synthesized, respectively. To achieve the etomidate-like target compound 8, compound 7 containing chloroacetamide group was firstly synthesized from starting compound 1, and this compound reacted with ethyl-1H-imidazole-5-carboxylate. The structures of the newyl synthesized 12 compounds were characterized and confirmed by FT-IR, MALDI-TOF/MS, 1H NMR, 13C NMR.Within the scope of in silico study, ligand binding status of all compounds on the GABAA receptor was revealed. Molecular docking studies of them with GABAA found out that the interaction modes, including van der Waals interactions, hydrogen bonds, and pi-pi interactions, are similar to that of the cocrystalline ligand Propofol. For the compounds 1, 2, 3, 4 d, 5, 7 have micromolar (mu M) level, for the compounds 4 a, 4 b, 4 c, 4 e, 4 f, 6 and 8 have nanomolar (nM) level of inhibition has been estimated. When all data such as active localization, interacting residues, bond types formed, estimated Ki values, docking scores are evaluated together, compounds 1, 2, 3 and 7 which can be considered as synthesis starting or intermediate material, may be less effective.On the other hand the anticancer activities of the synthesized compounds were investigated against A549 (non-small cell lung carcinoma) and BEAS-2B cell line (normal bronchial epithelial) cell lines using Resazurin cell viability assay. It has been revealed that the compounds 4, 5, 6 and 8 may be more active in terms of anesthetic activity, whereas only compound 6 showed anti-cancer activity. In this study Propofol-like Schiff base and carbothioamide derivatives were synthesized and characterized. Anesthetic activity of the compounds was determined by molecular docking calculations with GABAA. In addition, anticancer activities of the synthesized compounds were investigated against A549 (non-small cell lung carcinoma) and BEAS-2B cell line (normal bronchial epithelial) cell lines using Resazurin cell viability assay, and compound 6 exhibited anti-cancer activity with an IC50 value of 107.71 +/- 6.96. image

This study aimed to investigate the effect of propolis on pyruvate kinase (PK) which is a key enzyme in glycolysis and superoxide dismutase (SOD), an antioxidant enzyme on toxicity induced by DOX in different tissues. Using molecular docking, It was looked into how propolis affected the enzymes responsible for glycolysis and the antioxidant system. There was no application in the first group (control). The second group received 100 mg·kg-1 day of propolis by gavage needle for 7 days, a single dose of 20 mg·kg-1 intraperitoneal DOX to the third group, and propolis+DOX to the fourth group. Two days prior to DOX administration, propolis application began, and it lasted for seven days. PK and SOD activities were determined in liver, heart, kidney, and testis tissues, and molecular docking was applied to ratify the activity of some propolis components (caffeic acid phenethyl ester (CAPE) and Quercetin) on PK and SOD enzymes. When the DOX group was compared with the control group, a decrease in PK and SOD activities were found, and significant difference was found in PK and SOD activities. Administration of DOX decreased PK and SOD activities of liver, heart, kidney, and testis tissues. In conclusion, our study reveals that DOX disrupts glycolysis in rat tissues. CAPE and Quercetin compounds were shown to interact similarly with the cocrystal ligands of PK and SOD. In addition, when the interaction types of these compounds especially on PK and the docking scores obtained were examined, it can be said that they show higher affinity than DOX.

The tendency toward natural herbal products has increased due to the antibiotic resistance developed by microorganisms and the severe side effects of antibiotics commonly used in infectious diseases worldwide. Although antimicrobial studies have been conducted with several species of the Iris genus, this study is the first in the literature to be performed with Iris persica L. subsp. persica aqueous and methanol extracts. In this study, the phenolic content of I. persica was determined by LC–MS/MS analysis, the in vitro antimicrobial activity of I. persica aqueous and methanol extracts was examined, and this study was supported by in silico analysis. Consequently, methanol and aqueous extracts were observed to have inhibitory effects against all tested microorganisms except Candida krusei. Although the MIC values of aqueous extract and methanol extract against Staphylococcus aureus and Klebsiella pneumoniae are the same (22.5 and 11.25 mg/mL, respectively), the inhibitory effect of aqueous extract is generally more potent (MIC value is 11.25 mg/mL for Candida parapsilosis and other bacterial species, and 90 mg/mL for Candida albicans and Candida tropicalis) than that of methanol extract. In silico results showed that hydroxybenzaldeyde, vanillin, resveratrol, isoquercitrin, kaempferol‐3‐glucoside, fisetin, and luteolin were more prone to antifungal activity. Hence, shikimic, gallic, protocatechuic, vanillic, caffeic, o‐coumaric, trans‐ferulic, sinapic acids, and hesperidin were more prone to antibacterial activity. In vitro and in silico results show that the antibacterial activity of our extracts may be higher than the antifungal activity. This preliminary study indicates the anti‐infective potential of I. persica extracts and their usability in medicine and pharmacology.

Monoamine oxidase (MAO) is an enzyme that helps regulate the functions of intracellular amines, as well as chemicals such as dopamine, serotonin and norepinephrine, in the brain and its tissues. Active substances that are inhibitors of monoamine oxidases (MAOs) are used in the treatment of anxiety, depression and Alzheimer’s disease. Previous studies have shown that compounds containing piperazine rings show MAO-A inhibitory activity. Based on these studies, 4 compounds containing piperazine and benzothiazole rings were designed, and the structures of the compounds were elucidated using spectroscopic methods such as HRMS and 1H-NMR. hMAO-A and hMAO-B inhibitory activity was examined by in vitro methods. An in silico procedure was applied to investigate the residues and binding modes that interact with the docking of compounds 3a-d to the active site of the hMAO-A (PDB ID: 2Z5X) enzyme identified in the previous study. Compound 3b was found to be the most effective agent among the synthesized compounds with an IC50 value of 0.104±0.004 µM against the MAO-A enzyme.

Secondary metabolites obtained from plants are among the most commonly encountered chemotherapeutics used in cancer treatment. Plants contain thousands of metabolites; therefore, it is important to reach the compound primarily responsible for activity by fractionating plant extracts through activity-guided isolation. The cytotoxic activities of C. saligna fractions, sub-fractions, and all pure compounds obtained from the plant were investigated in vitro using MCF-7 (human breast cancer), HeLa (human cervical cancer), and PC-3 (prostate cancer) cell lines. Eighteen compounds were isolated from C. saligna, comprising eight sesquiterpene lactones, three flavonoids, five lignans, and two phenolic compounds, with their structures elucidated through 1H-NMR, 13C-NMR, and HMBC spectroscopic techniques. The molecular docking scores of the pure compounds obtained from these sub-fractions were determined using both AutoDock and AutoDock Vina programs. It has been proven that the affinities of linichlorin B and aguerin B for Bcl-2 are higher than those of other compounds, considering the calculated Ki values and placement scores. Notable activities of linichlorin B, cynaropicrin, and aguerin B (with IC50 values of 13.67 μg/ml, 6.79 μg/ml, and 3.46 μg/ml, respectively) were detected in the PC-3 cell line; aguerin B demonstrated activity most comparable to the standard anticancer agent doxorubicin. Likewise, linichlorin B, aguerin B, and cynaropicrin demonstrated notable efficacy in the HeLa and MCF-7 cell lines, as reported by the American National Cancer Institute. Aguerin B, linichlorin B, and cynaropicrin are projected to serve as promising novel chemotherapeutic agents for cancer therapy.

Alzheimer’s disease is a progressive and degenerative brain disease that negatively affects people’s lives and reduces cognitive and sensory human functions. Today, there are active ingredients that work on Alzheimer’s disease, containing benzodioxole and thiadiazole rings. Acetylcholinesterase terminates neurotransmission in the nervous system and leads to the accumulation of acetylcholine, overstimulation of various receptors and consequent impairment of neurotransmission. Thiadiazole and benzodioxole rings are compounds that exhibit a wide range of biological activities, especially known to be effective on acetylcholinesterase. A new compound containing benzodioxole and thiadiazole rings was designed, synthesized and its chemical structure was revealed using spectroscopic methods such as HRMS, 13C-NMR and 1H-NMR. Acetylcholinesterase inhibition activities were investigated using in vitro methods. To elucidate the acetylcholinesterase inhibition of compound 4a, it was subjected to in silico insertion procedure with 4EY7. Compound 4a exhibited 0.114±0.005 µM against AChE. The above data is compared with data for donepezil (0.0201±0.0014 µM), the reference compound in our study.