{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:58:19Z","timestamp":1791665899915,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union","award":["BG-RRP-2.004-0002"],"award-info":[{"award-number":["BG-RRP-2.004-0002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>[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 \u03bcg\/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 \u03bcg\/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.<\/jats:p>","DOI":"10.3390\/molecules28135034","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:45:11Z","timestamp":1687913111000},"page":"5034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fused Triazinobenzimidazoles Bearing Heterocyclic Moiety: Synthesis, Structure Investigations, and In Silico and In Vitro Biological Activity"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-0567","authenticated-orcid":false,"given":"Kameliya","family":"Anichina","sequence":"first","affiliation":[{"name":"Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-9361","authenticated-orcid":false,"given":"Nikolai","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Lumov","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 9, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitar","family":"Vuchev","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Parasitology and Tropical Medicine, Medical University, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galya","family":"Popova-Daskalova","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Parasitology and Tropical Medicine, Medical University, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgi","family":"Momekov","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1097-1850","authenticated-orcid":false,"given":"Emiliya","family":"Cherneva","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 9, 1113 Sofia, Bulgaria"},{"name":"Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rositsa","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anelia","family":"Mavrova","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1239-3249","authenticated-orcid":false,"given":"Stela","family":"Atanasova-Vladimirova","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry, Bulgarian Academy of Sciences, Build. 11, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iskra","family":"Piroeva","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry, Bulgarian Academy of Sciences, Build. 11, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-9681","authenticated-orcid":false,"given":"Denitsa","family":"Yancheva","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 9, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4274\/balkanmedj.2017.0167","article-title":"Human Parasitic Diseases in Bulgaria in between 2013\u20132014","volume":"35","author":"Rainova","year":"2018","journal-title":"Balk. Med. J."},{"key":"ref_2","unstructured":"European Centre for Disease Prevention and Control (2022). ECDC. Annual Epidemiological Report for 2020, ECDC. Available online: https:\/\/www.ecdc.europa.eu\/sites\/default\/files\/documents\/Trichinellosis-AER_2020_Final.pdf."},{"key":"ref_3","first-page":"251","article-title":"Progress in Treatment and Prevention of Trichinellosis","volume":"3","author":"Yu","year":"2015","journal-title":"J. Infect. Dis. 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