![In silico profilirovanie proizvodnykh 3,4-digidro-1H-[1,4]oksazino[4,3-a]benzimidazola: prognoz tsitotoksicheskikh svoistv i ADME-profilya](/upload/12631c5e396938a702bdd516ae8c4208/issues/cover/46d313f15c627c07a1f9586efd8784d2.png)
A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences
Yaroslavl, Yaroslavl, Russian Federation
P.G. Demidov Yaroslavl State University
Yaroslavl, Yaroslavl, Russian Federation
A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences
Yaroslavl, Yaroslavl, Russian Federation
from 01.01.2025 until now
P.G. Demidov Yaroslavl State University (Student)
Yaroslavl, Yaroslavl, Russian Federation
P.G. Demidov Yaroslavl State University (Associate Professor)
Yaroslavl, Yaroslavl, Russian Federation
P.G. Demidov Yaroslavl State University
Yaroslavl, Yaroslavl, Russian Federation
A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences
Yaroslavl, Yaroslavl, Russian Federation
V predyduschih rabotah nami byl sintezirovan ryad proizvodnyh 3,4-digidro-1H-oksazino[4,3-a]benzimidazola, vklyuchaya ranee ne opisannye v literature soedineniya, putem funkcionalizacii proizvodnogo benzimidazola s annelirovannym morfolinovym ciklom v reakcii SEAr. S cel'yu ocenki ih potenciala kak farmacevticheskih substanciy proveden in silico analiz citotoksicheskogo profilya i farmakokineticheskih parametrov. Prognoziruemaya citotoksichnost' vyyavila vysokuyu veroyatnost' toksicheskogo vozdeystviya na nervnuyu i dyhatel'nuyu sistemy dlya soedineniy s klassami toksichnosti ot II do IV i LD50 v diapazone 10-1500 mg/kg. Poluchennye dannye predpolagayut potencial'nyy protivoopuholevyy effekt soedineniy v otnoshenii gliom i raka legkih. Analiz ADME-profilya soedineniy pokazal sootvetstvie vseh molekul pravilu Lipinskogo, chto delaet celesoobraznym dal'neyshee issledovanie ih protivoopuholevogo potenciala v in vitro issledovaniyah.
kondensirovannye proizvodnye benzimidazola, morfolinovyy cikl, prognozirovanie citotoksicheskogo profilya, farmacevticheskaya aktivnost' ocenka farmakokineticheskih parametrov
1. Ersan R.H., Kuzu B., Yetkin D., Alagoz M.A., Dogen A., Burmaoglu S. 2-Phenyl substituted Benzimidazole derivatives: Design, synthesis, and evaluation of their antiproliferative and antimicrobial activities. Med. Chem. Res, 2022, 16(31), 1192-1208. DOI:https://doi.org/10.1007/s00044-022-02900-3. EDN: https://elibrary.ru/HATCZA
2. Pham E.C., Le Thi T.V., Ly Hong H.H., Vo Thi B.N., Vong L.B., Vu T.T., Vo D.D., Tran Nguyen N.V., Bao Le K.N., Truong T.N. N,2,6-Trisubstituted 1H-benzimidazole derivatives as a new scaffold of antimicrobial and anticancer agents: design, synthesis, in vitro evaluation, and in silico studies. RSC Adv., 2022, 13(1), 399 420. DOIhttps://doi.org/10.1039/d2ra06667j. EDN: https://elibrary.ru/NXICQY
3. Bansal S., Gaur R., Bhardwaj H., Kumar N., Sharma G.K., Mishra S.S. Synthesis, biological evaluation, and molecular docking studies of benzimidazole derivatives substitutes as new antimicrobial agents. JDDMC, 2024, 10(2), 54-66. DOIhttps://doi.org/10.11648/j.jddmc.20241002.12. EDN: https://elibrary.ru/WSFDGG
4. Ahmed A.E.R., Hassan Y.A.-E. Benzimidazole derivatives as potential chemotherapeutic agents. Curr. Drug Ther. 2013, 8(1), 1-14. DOI:https://doi.org/10.2174/1574885511308010001 EDN: https://elibrary.ru/YDQRWH
5. Akhtar W., Khan M.F., Verma G., Shaquiquzzaman M., Rizvi M.A., Mehdi S.H., Akhter M., Alam M.M. Therapeutic evolution of benzimidazole derivatives in the last quinquennial period. Eur. J. Med. Chem., 2017, 126, 705-753. DOI:https://doi.org/10.1016/j.ejmech.2016.12.010 EDN: https://elibrary.ru/XZMBET
6. Begunov R.S., Egorov D.O., Chetvertakova A.V., Savina L.I., Zubishina A.A. Antibakterial'naya aktivnost' galogen- i nitroproizvodnyh benzimidazola v otnoshenii Bacillus subtilis. Antibiotiki i himioter., 2023, 68(3-4), 19-24. DOI:https://doi.org/10.37489/0235-2990-2023-68-3-4-19-24. EDN: https://elibrary.ru/BMKHKH
7. Begunov R.S., Zayceva Yu.V., Sokolov A.A., Egorov D.O., Filimonov S.I. Sintez i antibakterial'naya aktivnost' 1,2,3,4-tetragidro- i pirido[1,2-a]benzimidazolov. Him. farm. zhurnal, 2022, 56(1), 25-31. DOI:https://doi.org/10.30906/0023-1134-2022-56-1-25-31 EDN: https://elibrary.ru/FCHEAJ
8. Nandwana N.K., Singh R.P., Patel O.P.S., Dhiman S., Saini H.K., Jha P.N., Kumar A. Design and Synthesis of Imidazo/Benzimidazo[1,2-c]quinazoline Derivatives and Evaluation of Their Antimicrobial Activity. ACS Omega, 2018, 3(11), 16338-16346. DOI:https://doi.org/10.1021/acsomega.8b01592.
9. Mohamed B.G., Abdel-Alim A.M., Hussein M.A. Synthesis of 1-acyl-2-alkylthio-1,2,4-triazolobenzimidazoles with antifungal, anti-inflammatory and analgesic effects. Acta Pharm., 2006, 56(1), 31-48.
10. Huo X., Hou D., Wang H., He B., Fang J., Meng Y., Liu L., Wei Z., Wang Z., Liu F.W. Design, synthesis, in vitro and in vivo anti-respiratory syncytial virus (RSV) activity of novel oxizine fused benzimidazole derivatives. Eur. J. Med. Chem., 2021, 224, Article 113684. DOI:https://doi.org/10.1016/j.ejmech.2021.113684. EDN: https://elibrary.ru/OZOQKN
11. Wang H., Meng Y., Yang J., Huang H., Zhao Y., Zhu C., Wang C., Liu F.W. Design, synthesis and antitumour activity of novel 5(6)-amino-benzimidazolequinones containing a fused morpholine. Eur. J. Med. Chem., 2022, 238, Article 114420. DOI:https://doi.org/10.1016/j.ejmech.2022.114420. EDN: https://elibrary.ru/NLXEXR
12. Aleksandrova Y., Savina L., Shagina I., Lyubina A., Zubishina A., Makarova S., Bagylly A., Khokhlov A., Begunov R., Neganova M. New Dihalogenated Derivatives of Condensed Benzimidazole Diones Promotes Cancer Cell Death Through Regulating STAT3/HK2 Axis/Pathway. Molecules, 2025, 30(21), 4150. DOI:https://doi.org/10.3390/molecules30214150 EDN: https://elibrary.ru/EFUFIH
13. Begunov R.S., Aleksandrova Yu.R., Shagina I.A., Kucherenko M.V., Pelevin P.S., Hohlov A.L., Neganova M.E. Citotoksichnost' novogo kondensirovannogo proizvodnogo benzimidazoldiona v otnoshenii liniy kletok opuholevogo i normal'nogo proishozhdeniya. Acta Biomedica Scientifica, 2025, 10(6), 12-19. DOI:https://doi.org/10.29413/ABS.2025-10.6.2 EDN: https://elibrary.ru/OZXASW
14. Sondhi S.M., Rajvanshi S., Johar M., Bharti N., Azam A., Singh A.K. Anti-inflammatory, analgesic and antiamoebic activity evaluation of pyrimido[1,6-a]benzimidazole derivatives synthesized by the reaction of ketoisothiocyanates with mono and diamines. Eur. J. Med. Chem., 2002, 37(10), 835-843. DOI:https://doi.org/10.1016/s0223-5234(02)01403-4.
15. Sondhi S. M., Rani R., Singh J., Roy P., Agrawal S. K., Saxena A. K. Solvent free synthesis, anti-inflammatory and anticancer activity evaluation of tricyclic and tetracyclic benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2010, 20(7), 2306-2310. DOI:https://doi.org/10.1016/j.bmcl.2010.01.147. EDN: https://elibrary.ru/NAKOUH
16. Begunov R.S., Savina L.I., Astaf'eva D.A. Vnutrimolekulyarnoe aminirovanie orto-nitro-tret-anilinov kak odin iz putey sinteza kondensirovannyh proizvodnyh benzimidazola s uzlovym atomom azota. Ot himii k tehnologii shag za shagom, 2025, 6(1), 22-33. DOI:https://doi.org/10.52957/2782-1900-2025-6-1-22-33 EDN: https://elibrary.ru/YUCJVL
17. Kucherenko M.V., Savina L.I., Begunov R.S., Zubishina A.A., Gracheva E.L. Regioselektivnost' reakcii SEAr 8-hlor-3,4-digdro-1H-[1,4]oksazino[4,3-a]benzimidazola. Ot himii k tehnologii shag za shagom, 2025, 6(4), 60-71. DOI:https://doi.org/10.52957/2782-1900-2025-6-4-60-71 EDN: https://elibrary.ru/OTRRTW
18. Balani S.K., Miwa G.T., Gan L.S., Wu J.T., Lee F.W. Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection. Curr Top Med Chem. 2005, 5(11), 1033-1038. DOIhttps://doi.org/10.2174/156802605774297038
19. Daina A., Michielin O., Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7, Article 42717. DOI:https://doi.org/10.1038/srep42717 EDN: https://elibrary.ru/YZSVSD
20. Manikandan P., Nagini S. Cytochrome P450 Structure, Function and Clinical Significance: A Review. Curr Drug Targets. 2018, 19(1), 38-54. DOIhttps://doi.org/10.2174/1389450118666170125144557
21. Banerjee P., Kemmler E., Dunkel M., Preissner R. ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res., 2024, 52(W1), W513-W520. DOI:https://doi.org/10.1093/nar/gkae303 EDN: https://elibrary.ru/GXCWJQ
