Synthesis, Cytotoxic Activity Evaluation and Molecular Docking Studies of Some Benzimidazole Derivatives

Aybüke Züleyha Kaya; Derya Osmaniye; Asaf Evrim Evren; Leyla Yurttaş; Şeref Demirayak

doi:10.17776/csj.1392037

EN

Synthesis, Cytotoxic Activity Evaluation and Molecular Docking Studies of Some Benzimidazole Derivatives

Abstract

In this study, the synthesis of 2-(2-acetyl-1H-benzimidazol-1-yl)-1-arylethanone (3a-3d) and 1-methyl-3-phenyl-benzo[4,5]imidazo[1,2-a]pyrazine derivatives (4a-4d) and to investigate their cytotoxic activity were aimed. APCI, IR, 1HNMR, and 13CNMR spectra were utilized to determine the structure of the synthesized compounds. The cytotoxic activity of selected compounds were detected in A549 (human lung carcinoma) and NIH3T3 (mouse embryonic fibroblasts) cell lines. Compounds 4c and 4d were found to be selectively cytotoxic against A549 and NIH3T3 cell lines. Molecular docking studies were performed using the data retrieved from the Protein Data Bank server (PDBID: 4QTX).

Keywords

Thanks

Our authors express their gratitude to the Herbal, Pharmaceutical, and Scientific Research Application and Research Center (AUBİBAM).

References

[1] M. Hou, H.C. Li, N. An, S.Y. Pang, W.G. Li, J. Tong, Synthesis, crystal structures and anticancer studies of Ni (Ⅱ), Co (Ⅲ) and Zn (Ⅱ) complexes based on 5-bromosalicylaldehyde- 2-(2-aminophenyl)benzimidazole Schiff base, J. Mol. Struct., 1294 (2023) 136500.
[2] The top 10 causes of death, (n.d.). https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death (accessed November 15, 2023).
[3] D. Nuha, A.E. Evren, Z.Ş. Çiyanci, H.E. Temel, G. Akalin Çiftçi, L. Yurttaş, Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5‐nitrothiophene derivatives for anticancer activity, Arch Pharm (Weinheim), 355 (2022).
[4] İ. Celik, G. Ayhan-Kılcıgil, B. Guven, Z. Kara, A.S. Gurkan-Alp, A. Karayel, A. Onay-Besikci, Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors, Eur. J. Med. Chem., 173 (2019) 240–249.
[5] A.E. Evren, L. Yurttaş, B. Eksellı, G. Akalın-Cıftcı, Novel Tri-substituted Thiazoles Bearing Piperazine Ring: Synthesis and Evaluation of their Anticancer Activity, Lett Drug Des Discov 16 (2019) 547–555. https://doi.org/10.2174/1570180815666180731122118. A. Sharma, V. Luxami, K. Paul, Purine-benzimidazole hybrids: Synthesis, single crystal determination and in vitro evaluation of antitumor activities, Eur. J. Med. Chem., 93 (2015) 414–422.
[6] G. Satija, B. Sharma, A. Madan, A. Iqubal, M. Shaquiquzzaman, M. Akhter, S. Parvez, M.A. Khan, M.M. Alam, Benzimidazole based derivatives as anticancer agents: Structure activity relationship analysis for various targets, J. Heterocycl Chem., 59 (2022) 22–66.
[7] R. Singla, K.B. Gupta, S. Upadhyay, M. Dhiman, V. Jaitak, Design, synthesis and biological evaluation of novel indole-benzimidazole hybrids targeting estrogen receptor alpha (ER-α), Eur. J. Med. Chem., 146 (2018) 206–219..
[8] T.S. Reddy, H. Kulhari, V.G. Reddy, V. Bansal, A. Kamal, R. Shukla, Design, synthesis and biological evaluation of 1,3-diphenyl-1 H -pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents, Eur. J. Med. Chem., 101 (2015) 790–805.

[9] M.L. Di Gioia, R. Cassano, P. Costanzo, N. Herrera Cano, L. Maiuolo, M. Nardi, F.P. Nicoletta, M. Oliverio, A. Procopio, Green Synthesis of Privileged Benzimidazole Scaffolds Using Active Deep Eutectic Solvent, Molecules, 24 (2019) 2885.
[10] K. Laxmikeshav, A. Himaja, N. Shankaraiah, Exploration of benzimidazoles as potential microtubule modulators: An insight in the synthetic and therapeutic evolution, J. Mol. Struct., 1253 (2022) 132251.
[11] N. Shrivastava, Mohd.J. Naim, Md.J. Alam, F. Nawaz, S. Ahmed, O. Alam, Benzimidazole Scaffold as Anticancer Agent: Synthetic Approaches and Structure–Activity Relationship, Arch Pharm (Weinheim), 350 (2017).
[12] Y.T. Lee, Y.J. Tan, C.E. Oon, Benzimidazole and its derivatives as cancer therapeutics: The potential role from traditional to precision medicine, Acta. Pharm. Sin. B, 13 (2023) 478–497.
[13] W. Hou, W. Dai, H. Huang, S.-L. Liu, J. Liu, L.-J. Huang, X.-H. Huang, J.-L. Zeng, Z.-W. Gan, Z.-Y. Zhang, J.-X. Lan, Pharmacological activity and mechanism of pyrazines, Eur. J. Med. Chem., 258 (2023) 115544.
[14] Ş. Demirayak, L. Yurttaş, Synthesis and anticancer activity of some 1,2,3-trisubstituted pyrazinobenzimidazole derivatives, J. Enzyme Inhib. Med. Chem., 29 (2014) 811–822.
[15] W.R. Siegart, A.R. Day, Metabolite Analogs. VII. Preparation of Some Benzimidazolyl Analogs of Ethyl Pteroylglutamate, J. Am. Chem. Soc., 79 (1957) 4391–4394..
[16] G. Cheeseman, 2-ACETYLBENZIMIDAZOLE, J. Chem. Soc., (1964).
[17] S. Demirayak, K. Güven, Synthesis of some pyrido- and pyrazino-benzimidazole derivatives and their antifungal activity., Pharmazie, 50 (1995) 527–9.
[18] Demirayak S, Abu Mohsen U., Anticancer and anti-HIV activities of some pyrido/pyrazino-benzimidazole derivatives, Acta Pharm. Turc., 40 (1998) 9–12.
[19] M. V. Berridge, P.M. Herst, A.S. Tan, Tetrazolium dyes as tools in cell biology: New insights into their cellular reduction, (2005) 127–152.
[20] D. Osmaniye, S. Levent, C.M. Ardıç, Ö. Atlı, Y. Özkay, Z.A. Kaplancıklı, Synthesis and anticancer activity of some novel benzothiazole-thiazolidine derivatives, Phosphorus Sulfur Silicon Relat. Elem., 193 (2018) 249–256.
[21] D. Osmaniye, B. Korkut Çelikateş, B.N. Sağlık, S. Levent, U. Acar Çevik, B. Kaya Çavuşoğlu, S. Ilgın, Y. Özkay, Z.A. Kaplancıklı, Synthesis of some new benzoxazole derivatives and investigation of their anticancer activities, Eur. J. Med. Chem., 210 (2021) 112979.
[22] D. Osmaniye, S. Levent, A. Karaduman, S. Ilgın, Y. Özkay, Z. Kaplancıklı, Synthesis of New Benzothiazole Acylhydrazones as Anticancer Agents, Molecules, 23 (2018) 1054.
[23] A.E. Evren, D. Nuha, L. Yurttaş, Focusing on the moderately active compound (MAC) in the design and development of strategies to optimize the apoptotic effect by molecular mechanics techniques, European Journal of Life Sciences, 1 (2023) 118–126.
[24] Protein Data Bank, (n.d.).
[25] Schrödinger Release. 2020-3, Maestro. Schrödinger, LLC, New York, NY, USA; 2020., (n.d.).
[26] LigPrep module, Schrödinger Release. 2020-3, Maestro. Schrödinger, LLC, New York, NY, USA; 2020., (n.d.).
[27] A.E. EVREN, S. DAWBAA, D. NUHA, Ş.A. YAVUZ, Ü.D. GÜL, L. YURTTAŞ, Design and synthesis of new 4-methylthiazole derivatives: In vitro and in silico studies of antimicrobial activity, J. Mol. Struct., 1241 (2021) 130692.
[28] Glide module, Schrödinger Release 2020-3, Glide, Schrödinger, LLC, New York, NY, USA (2020), (n.d.).

Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Aybüke Züleyha Kaya ^*
0009-0002-1614-2380
Türkiye

Derya Osmaniye
0000-0002-0499-436X
Türkiye

Asaf Evrim Evren
0000-0002-8651-826X
Türkiye

Leyla Yurttaş
0000-0002-0957-6044
Türkiye

Şeref Demirayak
0000-0002-0841-1299
Türkiye

Publication Date

March 28, 2024

Submission Date

November 16, 2023

Acceptance Date

March 12, 2024

Published in Issue

Year 2024 Volume: 45 Number: 1

DOI

https://doi.org/10.17776/csj.1392037

IZ

https://izlik.org/JA42LZ23UC

Cite

RIS / Bibtex

APA

Kaya, A. Z., Osmaniye, D., Evren, A. E., Yurttaş, L., & Demirayak, Ş. (2024). Synthesis, Cytotoxic Activity Evaluation and Molecular Docking Studies of Some Benzimidazole Derivatives. Cumhuriyet Science Journal, 45(1), 80-87. https://doi.org/10.17776/csj.1392037