Browsing by Author "Momekov G."

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    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.
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    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.
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    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.
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    Peptide-based targeted cancer therapeutics: Design, synthesis and biological evaluation
    (2022-09-01) Iwanov I.; Rossi A.; Montesi M.; Doytchinova I.; Sargsyan A.; Momekov G.; Panseri S.; Naydenova E.
    Cancer is the leading cause for human mortality together with cardiovascular diseases. Abl (Abelson) tyrosine kinases play a fundamental role in transducing various signals that control proliferation, survival, migration and invasion in several cancers such as Chronic Myeloid Leukemia (CML), breast cancer and brain cancer. For these reasons Abl tyrosine kinases are considered important biological targets in drug discovery. In this study a series of lysine-based oligopeptides with expected Abl inhibitory activity were designed resembling the binding of FDA-approved drugs (i.e. of Imatinib and Nilotinib), synthesized, purified by High Performance Liquid Chromatography (HPLC), analyzed by mass spectrometry (MS) and biologically tested in vitro in CML (AR-230 and K-562), breast cancers (MDA-MB 231 and MDA-MB 468) and glioblastoma cell lines (U87 and U118). The solid-phase peptide synthesis (SPPS) by Fmoc (9-fluorenylmethoxycarbonyl) chemistry was used to synthesize target compounds. AutoDock Vina was applied for simulation binding to Abl. The biological activities were measured evaluating cytotoxic effect, induction of apoptosis and inhibition of cancer cells migration. The new peptides exhibited different concentration-dependent antiproliferative effect against the tumor cell lines after 72 h treatment. The most promising results were obtained with the U87 glioblastoma cell line where a significant reduction of the migration ability was detected with one compound (H-Lys1-Lys2-Lys3-NH2).
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    Synthesis of a new polynuclear platinum (II) complex and its prodrug forms. evaluation of their cytotoxic properties
    (2013-05-21) Mitova V.; Bogomiloval A.; Shestakova P.; Momekov G.; Momekova D.; Abbas R.; Koseva N.
    The present study is focused on the synthesis of a dinuclear platinum(II) complex containing two polyamino ligands - spermidine and diaminohexane and its prodrug forms. The latter were prepared via reaction with phosphonates- the low molecular dimethyl hydrogen phosphonate and poly(oxyethylene hydrogen phosphonate).The newly obtained compounds were isolated and characterized applying 1H, 31P and 195Pt NMR spectroscopy. The cytotoxic activities of the low molecular complexes were determined in vitro by MTT method against a panel of human tumor cell lines. The synthesized complex, a derivative of BBR3571, causes 50 % inhibition of cellular viability in tumor cells at micromolar concentrations and effectively by-pass the resistance mechanisms in a cisplatin-refractory cell line.