Synthesis, molecular docking, and in vitro tests of the Mannich base derivatives of Benzimidazolvanilin as an anti-inflammatory

Authors

Inas Priasti Siwi , Hayun , Arry Yanuar

DOI:

10.29303/jppipa.v10i4.6199

Published:

2024-04-25

Issue:

Vol. 10 No. 4 (2024): April

Keywords:

Benzimidazolvanilin, Mannich base, Anti-inflammatory, Molecular docking

Research Articles

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Siwi, I. P., Hayun, & Yanuar, A. (2024). Synthesis, molecular docking, and in vitro tests of the Mannich base derivatives of Benzimidazolvanilin as an anti-inflammatory . Jurnal Penelitian Pendidikan IPA, 10(4), 1760–1769. https://doi.org/10.29303/jppipa.v10i4.6199
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Abstract

Benzimidazole and vanillin are compounds which can act as anti-inflammatory. However, the potential of these two compounds is still low. The structure of benzimidazole and vanillin was combined with Mannich base substitution in order to increase potency and selectivity as an anti-inflammatory. In this study, benzimidazolvanillin (1) and its Mannich base derivatives were synthesized. The synthesized compounds (2a-d) show anti-inflammatory activity based on in vitro tests by using protein denaturation inhibition test. Furthermore, the IC50 obtained ranged from 210 -243 μM. This potency is lower than diclofenac (IC50: 2,99μM). In molecular docking, the results of the inhibition constant ratio between COX-1 / COX-1 as well as the interaction of the ligand and target protein show that benzimimidazolvanillin and its Mannich-base derivatives could be anti-inflammatory drug candidates that should be investigated further.

References

Agu, P. C., Afiukwa, C. A., Orji, O. U., Ezeh, E. M., Ofoke, I. H., Ogbu, C. O., … Aja, P. M. (2023). Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-023-40160-2

Bindu, S., Mazumder, S., & Bandyopadhyay, U. (2020). Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochemical Pharmacology, 180, 114147. https://doi.org/10.1016/j.bcp.2020.114147

Boiko, Y. A., Nesterkina, M. V., Shandra, A. A., & Kravchenko, I. A. (2019). Analgesic and Anti-Inflammatory Activity of Vanillin Derivatives. Pharmaceutical Chemistry Journal, 53(7), 650–654. https://doi.org/10.1007/s11094-019-02056-2

Deb, P. K., Mailabaram, R. P., Al-Jaidi, B., & Saadh, M. J. (2017). Molecular Basis of Binding Interactions of NSAIDs and Computer-Aided Drug Design Approaches in the Pursuit of the Development of Cyclooxygenase-2 (COX-2) Selective Inhibitors. In Nonsteroidal Anti-Inflammatory Drugs, 2, 64. https://doi.org/10.5772/intechopen.68318

Faki, Y., & Er, A. (2021). Different chemical structures and physiological/pathological roles of cyclooxygenases. Rambam Maimonides Medical Journal, 12(1). https://doi.org/10.5041/RMMJ.10426

Forli, S., Huey, R., Pique, M. E., Sanner, M. F., Goodsell, D. S., & Olson, A. J. (2016). Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nature Protocols, 11(5), 905–919. https://doi.org/10.1038/nprot.2016.051

Gadhwal, M. K., Article, R., D’mello, P., Kumar Gadhwal, M., Joshi, U., & Shetgiri, P. (2011). Modeling of COX-2 inhibotory activity of flavonoids. In Article in International Journal of Pharmacy and Pharmaceutical Sciences, 3(4), 33-40. Retrieved from https://www.researchgate.net/publication/224054089

Geethapriya, C., & Elumalaiim, K. (2021). Mannichbases: An Overview Of Heterocyclic Compound With Various Biological Activities. International Journal of Pharmaceutical Sciences and Research, 12(12), 6151. https://doi.org/10.13040/IJPSR.0975-8232.12(12).6151-65

Janowska, S., Andrzejczuk, S., Gawryś, P., & Wujec, M. (2023). Synthesis and Antimicrobial Activity of New Mannich Bases with Piperazine Moiety. Molecules, 28(14). https://doi.org/10.3390/molecules28145562

Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3), 221–234. https://doi.org/10.1007/s10822-013-9644-8

Marinescu, M., Cintezǎ, L. O., Marton, G. I., Chifiriuc, M. C., Popa, M., Stǎnculescu, I., … Stavarache, C. E. (2020). Synthesis, density functional theory study and in vitro antimicrobial evaluation of new benzimidazole Mannich bases. BMC Chemistry, 14(1). https://doi.org/10.1186/s13065-020-00697-z

Mengle-Gaw, L. J., & Schwartz, B. D. (2002). Cyclooxygenase-2 inhibitors: Promise or peril? Mediators of Inflammation, 11, 275–286. https://doi.org/10.1080/09629350290000041

Michaux, C., de Leval, X., Julémont, F., Dogné, J. M., Pirotte, B., & Durant, F. (2006). Structure-based pharmacophore of COX-2 selective inhibitors and identification of original lead compounds from 3D database searching method. European Journal of Medicinal Chemistry, 41(12), 1446–1455. https://doi.org/10.1016/j.ejmech.2006.07.017

Orlando, B. J., & Malkowski, M. G. (2016). Substrate-selective inhibition of cyclooxygeanse-2 by fenamic acid derivatives is dependent on peroxide tone. Journal of Biological Chemistry, 291(29), 15069–15081. https://doi.org/10.1074/jbc.M116.725713

Owoloye, A. J., Ligali, F. C., Enejoh, O. A., Musa, A. Z., Aina, O., Idowu, E. T., & Oyebola, K. M. (2022). Molecular docking, simulation and binding free energy analysis of small molecules as Pf HT1 inhibitors. PLoS ONE, 17(8), e0268269. https://doi.org/10.1371/journal.pone.0268269

Pantsar, T., & Poso, A. (2018). Binding affinity via docking: Fact and fiction. Molecules, 23(8), 1899. https://doi.org/10.3390/molecules23081899

Pessoa-Mahana, D., Espinosa-Bustos, C., Mella-Raipán, J., Canales-Pacheco, J., & Pessoa-Mahana, H. (2009). Microwave-assisted synthesis and regioisomeric structural elucidation of novel benzimidazo[1,2d][1,4]benzodiazepinone derivatives. General Papers ARKIVOC, 131–140. Retrieved from https://repositorio.uchile.cl/handle/2250/120942

Puppala, N., & Reddy, G. A. (2020). Review on Effects of NSAID`S on Different Systems. Asian Journal of Pharmaceutical Research and Development, 8(1), 100–109. https://doi.org/10.22270/ajprd.v8i1.621

Rahmawati, N., Hariyanti, H., Saputri, F. C., & Hayun, H. (2020). Synthesis and preliminary in vitro anti-inflammatory evaluation of mannich bases derivatives of 4’-methoxy-substituted of asymmetrical cyclovalone analogs. Indonesian Journal of Pharmacy, 31(1), 35–41. https://doi.org/10.14499/indonesianjpharm31iss1pp35

Rimon, G., Sidhu, R. S., Lauver, D. A., Lee, J. Y., Sharma, N. P., Yuan, C., … Smith, W. L. (2010). Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1. Proceedings of the National Academy of Sciences of the United States of America, 107(1), 28–33. https://doi.org/10.1073/pnas.0909765106

Roman, G. (2015). Mannich bases in medicinal chemistry and drug design. European Journal of Medicinal Chemistry, 89, 743–816. https://doi.org/10.1016/j.ejmech.2014.10.076

Rouzer, C. A., & Marnett, L. J. (2020, August 12). Structural and Chemical Biology of the Interaction of Cyclooxygenase with Substrates and Non-Steroidal Anti-Inflammatory Drugs. Chemical Reviews, 120, 7592–7641. https://doi.org/10.1021/acs.chemrev.0c00215

Shivanika, C., Deepak Kumar, S., Ragunathan, V., Tiwari, P., Sumitha, A., & Brindha Devi, P. (2022). Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. Journal of Biomolecular Structure and Dynamics, 40(2), 585–611. https://doi.org/10.1080/07391102.2020.1815584

Torres, P. H. M., Sodero, A. C. R., Jofily, P., & Silva-Jr, F. P. (2019, September 2). Key topics in molecular docking for drug design. International Journal of Molecular Sciences, 20. https://doi.org/10.3390/ijms20184574

Vasuki B, Mahadevan N, Vijayabaskaran M, Mohanapriya K, Kosilamani P, Balaji K, … Sambathkumar R. (2021). An insight into the medicinal perspectives of mannich bases of benzimidazole derivatives: A review. International Journal of Research in Pharmaceutical Sciences, 12(3), 1895–1901. https://doi.org/10.26452/ijrps.v12i3.4790

Veerasamy, R., Roy, A., Karunakaran, R., & Rajak, H. (2021). Structure–activity relationship analysis of benzimidazoles as emerging anti-inflammatory agents: An overview. Pharmaceuticals, 14. https://doi.org/10.3390/ph14070663

Author Biographies

Inas Priasti Siwi, University of Indonesia

Hayun, University of Indonesia, Jakarta

Arry Yanuar, University of Indonesia, Jakarta

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