Browsing by Author "Cherneva E."
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Item 6-(Propan-2-yl)-3-methyl-morpholine-2,5-dione, a novel cyclodidepsipeptide with modulatory effect on rat thymocytes(2012-09-01) Pavlovic V.; Cherneva E.; Yancheva D.; Smelcerovic A.A study has been carried out on the potential effect of a novel cyclodidepsipeptide, 6-(propan-2-yl)-3-methyl-morpholine-2,5-dione (PMMD), on rat thymocytes. Rat thymocytes were cultivated with increasing PMMD concentrations (0.1, 1, 10 μg/well), for 24. h, and evaluated for proliferative activity, viability, reactive oxygen species and mitochondrial membrane potential. The higher PMMD concentrations inhibited thymocytes proliferative activity mainly through induction of oxidative stress and resulting cytotoxicity, without any mitochondrial membrane potential alterations in thymocytes. The obtained results are correlated with previously published data on effects of 6-(propan-2-yl)-4-methyl-morpholine-2,5-diones on rat thymocytes. The presence of methyl group in position 4 or/and the length of alkyl chain in position 3 of 6-(propan-2-yl)-morpholine-2,5-dione core plays a role for the obtained differences in the biological response between PMMD and two previously tested 6-(propan-2-yl)-4-methyl-morpholine-2,5-diones. © 2012 Elsevier Ltd.Item Effects on MC3T3-E1 cells and in silico toxicological study of two 6-(propan-2-yl)-4-methyl-morpholine-2,5-diones(2015-08-01) Vukelić-Nikolić M.; Kolarević A.; Tomović K.; Yancheva D.; Cherneva E.; Najman S.; Smelcerović A.Recently, we found that two cyclodidepsipeptides, 3,6-di-(propan-2-yl)-4-methyl-morpholine-2,5-dione (1) and 3-(2-methylpropyl)-6-(propan-2-yl)-4-methylmorpholine-2,5-dione (2), are excellent inhibitors of xanthine oxidase. In order to obtain more information about the toxicological potential of compounds 1 and 2 on bone cells, the current study was designed to evaluate the effect of these compounds on viability and proliferation of MC3T3-E1 cells. Compound 1 showed neither cytotoxic nor stimulatory effect on cell viability, while compound 2 showed a slight stimulatory effect on cell viability. Both studied compounds showed slight stimulatory effects on proliferation of MC3T3-E1 cells, in a dose dependent manner. Additionally, an in silico toxicological study of compounds 1 and 2 was performed, and the results indicate that they have a good probability of safe biological intake.Item Fused Triazinobenzimidazoles Bearing Heterocyclic Moiety: Synthesis, Structure Investigations, and In Silico and In Vitro Biological Activity(2023-07-01) Anichina K.; Georgiev N.; Lumov N.; Vuchev D.; Popova-Daskalova G.; Momekov G.; Cherneva E.; Mihaylova R.; Mavrova A.; Atanasova-Vladimirova S.; Piroeva I.; Yancheva D.[1,3,5]Triazino[1,2-a]benzimidazole-2-amines bearing heterocyclic moiety in 4-position were synthesized. The compounds were characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and HRMS spectroscopy. The molecular geometry and electron structure of these molecules were theoretically studied using density functional theory (DFT) methods. The molecular structure of the synthesized fused triazinobenzimidazole was confirmed to correspond to the 3,4-dihydrotriazinobenzimidazole structure through the analysis of spectroscopic NMR data and DFT calculations. The antinematodic activity was evaluated in vitro on isolated encapsulated muscle larvae (ML) of Trichinella spiralis. The results showed that the tested triazinobenzimidazoles exhibit significantly higher efficiency than the conventional drug used to treat trichinosis, albendazole, at a concentration of 50 μg/mL. The compound 3c substituted with a thiophen-2-yl moiety exhibited the highest anthelmintic activity, with a larvicidal effect of 58.41% at a concentration of 50 μg/mL after 24 h of incubation. Following closely behind, the pyrrole analog 3f demonstrated 49.90% effectiveness at the same concentration. The preliminary structure-anti-T. spiralis activity relationship (SAR) of the analogues in the series was discussed. The cytotoxicity of the benzimidazole derivatives against two normal fibroblast cells (3T3 and CCL-1) and two cancer human cell lines (MCF-7 breast cancer cells and chronic myeloid leukemia cells AR-230) was evaluated using the MTT-dye reduction assay. The screening results indicated that the compounds showed no cytotoxicity against the tested cell lines. An in silico study of the physicochemical and pharmacokinetic characteristics of the novel synthesized fused triazinobenzimidazoles showed that they were characterized by a significant degree of drug-likeness and optimal properties for anthelmintic agents.Item Fused Triazinobenzimidazoles Bearing Heterocyclic Moiety: Synthesis, Structure Investigations, and In Silico and In Vitro Biological Activity(2023-07-01) Anichina K.; Georgiev N.; Lumov N.; Vuchev D.; Popova-Daskalova G.; Momekov G.; Cherneva E.; Mihaylova R.; Mavrova A.; Atanasova-Vladimirova S.; Piroeva I.; Yancheva D.[1,3,5]Triazino[1,2-a]benzimidazole-2-amines bearing heterocyclic moiety in 4-position were synthesized. The compounds were characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and HRMS spectroscopy. The molecular geometry and electron structure of these molecules were theoretically studied using density functional theory (DFT) methods. The molecular structure of the synthesized fused triazinobenzimidazole was confirmed to correspond to the 3,4-dihydrotriazinobenzimidazole structure through the analysis of spectroscopic NMR data and DFT calculations. The antinematodic activity was evaluated in vitro on isolated encapsulated muscle larvae (ML) of Trichinella spiralis. The results showed that the tested triazinobenzimidazoles exhibit significantly higher efficiency than the conventional drug used to treat trichinosis, albendazole, at a concentration of 50 μg/mL. The compound 3c substituted with a thiophen-2-yl moiety exhibited the highest anthelmintic activity, with a larvicidal effect of 58.41% at a concentration of 50 μg/mL after 24 h of incubation. Following closely behind, the pyrrole analog 3f demonstrated 49.90% effectiveness at the same concentration. The preliminary structure-anti-T. spiralis activity relationship (SAR) of the analogues in the series was discussed. The cytotoxicity of the benzimidazole derivatives against two normal fibroblast cells (3T3 and CCL-1) and two cancer human cell lines (MCF-7 breast cancer cells and chronic myeloid leukemia cells AR-230) was evaluated using the MTT-dye reduction assay. The screening results indicated that the compounds showed no cytotoxicity against the tested cell lines. An in silico study of the physicochemical and pharmacokinetic characteristics of the novel synthesized fused triazinobenzimidazoles showed that they were characterized by a significant degree of drug-likeness and optimal properties for anthelmintic agents.Item Modulation Effect on Tubulin Polymerization, Cytotoxicity and Antioxidant Activity of 1H-Benzimidazole-2-Yl Hydrazones(2023-01-01) Argirova M.; Guncheva M.; Momekov G.; Cherneva E.; Mihaylova R.; Rangelov M.; Todorova N.; Denev P.; Anichina K.; Mavrova A.; Yancheva D.1H-benzimidazol-2-yl hydrazones with varying hydroxy and methoxy phenyl moieties were designed. Their effect on tubulin polymerization was evaluated in vitro on porcine tubulin. The compounds elongated the nucleation phase and slowed down the tubulin polymerization comparably to nocodazole. The possible binding modes of the hydrazones with tubulin were explored by molecular docking at the colchicine binding site. The anticancer activity was evaluated against human malignant cell lines MCF-7 and AR-230, as well as against normal fibroblast cells 3T3 and CCL-1. The compounds demonstrated a marked antineoplastic activity in low micromolar concentrations in both screened in vitro tumor models. The most active were the trimethoxy substituted derivative 1i and the positional isomers 1j and 1k, containing hydroxy and methoxy substituents: they showed IC50 similar to the reference podophyllotoxin in both tumor cell lines, accompanied with high selectivity towards the malignantly transformed cells. The compounds exerted moderate to high ability to scavenge peroxyl radicals and certain derivatives—1l containing metha-hydroxy and para-methoxy group, and 1b-e with di/trihydroxy phenyl moiety, revealed HORAC values high or comparable to those of well-known phenolic antioxidants. Thus the 1H-benisimidazol-2-yl hydrazones with hydroxy/methoxy phenyl fragments were recognized as new agents exhibiting promising combined antioxidant and antineoplastic action.Item Synthesis, crystal structure and biological activity screening of novel N-(α-bromoacyl)-α-amino esters containing valyl moiety(2015-01-01) Yancheva D.; Cherneva E.; Quick M.; Mikhova B.; Shivachev B.; Nikolova R.; Djordjevic A.; Untergehrer M.; Jürgenliemk G.; Kraus B.; Smelcerovic A.Three novel N-(α-bromoacyl)-α-amino esters: methyl 2-(2-bromo-3-methylbutanamido)pentanoate (1), methyl 2-(2-bromo-3-methylbutanamido)-2-phenylacetate (2) and methyl 2-(2-bromo-3-methylbutanamido)-3-phenylpropanoate (3) were synthesized. Single crystal X-ray diffraction data are reported for compounds 1 and 2. The cytotoxicity, antiinflammatory and antibacterial activity of compounds 1-3 were investigated. Additionally, the physico-chemical properties of studied compounds were calculated and an in silico toxicological study of compounds 1-3 was performed. The low level of cytotoxicity and absence of antibacterial and anti-inflammatory activity of 1-3 in tested concentrations might be a beneficial prerequisite for their incorporation in prodrugs.Item The effect of camphor and borneol on rat thymocyte viability and oxidative stress(2012-09-01) Cherneva E.; Pavlovic V.; Smelcerovic A.; Yancheva D.Camphor and borneol are wildly distributed in the essential oils of medicinal plants from various parts of the World. Our study has been carried out to evaluate the effect of these two bicyclic monoterpenes on rat thymocytes. Camphor and borneol at concentrations of 0.5 and 5 μg/mL did not induce significant toxicity on the immune system cells, while a significant increase of thymocyte viability was detected when cells were incubated with 50 μg/mL of camphor. A significant increase of cell viability was similarly detected when thymocytes were cultivated with borneol at concentrations of 0.5 and 5 μg/mL. The role of camphor and borneol in reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disturbances in rat thymocytes as well as their potential mechanism(s) of action were also discussed. © 2012 by the authors.