Synthesis and Anti-inflammatory Tests of 2-Hydroxy-N-(Pyridine-2-yl)Benzamide Mannich Base Substituted Morpholine and N-methyl piperazine

Authors

Gadis Anggraini , Hayun Hayun , Catur Jatmika

DOI:

10.29303/jppipa.v9i1.2319

Published:

2023-01-31

Issue:

Vol. 9 No. 1 (2023): January

Keywords:

Mannich base, Salicylamide analogs, Anti-inflammatory, Molecular docking

Research Articles

Downloads

How to Cite

Anggraini, G., Hayun, H., & Jatmika, C. . (2023). Synthesis and Anti-inflammatory Tests of 2-Hydroxy-N-(Pyridine-2-yl)Benzamide Mannich Base Substituted Morpholine and N-methyl piperazine. Jurnal Penelitian Pendidikan IPA, 9(1), 1–8. https://doi.org/10.29303/jppipa.v9i1.2319
Crossref
Scopus
Google Scholar
Europe PMC

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Abstract

Salicylic acid is a naturally active substance known to have anti-inflammatory and antioxidant activity, but it has side effects in the gastrointestinal tract. The modification of its carboxylic groups into amide derivatives can be a solution to overcome its weakness. This study synthesized salicylamide analogs, 2-hydroxy-N-(pyridine-2-yl)benzamide (1) and, its Mannich base derivatives. The synthesized compounds (2a-b) showed anti-inflammatory activity based on an in-vitro anti-inflammatory activity test using the inhibition protein denaturation method. The IC50 obtained was in the range of 0.121-0.145 mM. The potency was lower than piroxicam used as a standard compound (IC50 = 0.0073 mM). The molecular docking result shows that the ratio of COX-2/COX-1 binding affinity and ligand interaction of all synthesized compounds were not COX-2 selective.

References

Aqeel, M. T., Nisar-Ur-Rahman, Khan, A. U., Ahmad, A., Ashraf, Z., Rasheed, U., & Mansoor, S. (2020). Phenolic derivatives with antioxidant and anti-inflammatory activities: An in silico, in vitro and in vivo study. Pakistan Veterinary Journal, 39(4), 598–602. https://doi.org/10.29261/pakvetj/2019.052

Beny, R., Yana, N. R. A., & Leorita, M. (2020). Desain Turunan Senyawa Leonurine Sebagai Kandidat Obat Anti Inflamasi. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal), 6(1), 181–191. https://doi.org/10.22487/j24428744.2020.v6.i1.15025

Hayun, H., Gavrila, I., Silviana, S., Siahaan, A. E. K., Vonna, R. F., & Latifah, M. I. (2020). Synthesis and antioxidant activity study of new mannich bases derived from vanillic acid. Rasayan Journal of Chemistry, 13(1), 131–138. https://doi.org/10.31788/RJC.2020.1315300

Hayun, H., Maggadani, B. P., Kurnia, A., Hanifah, A., Yuliandi, M., Fitriyani, I., & Hadrianti, S. P. (2019). Anti-inflammatory and antioxidant activity of synthesized mannich base derivatives of (2e,6e)-2-[(4-hydroxy-3-methoxyphenyl)methylidene]-6-(phenyl methylidene)cyclohexan-1-one. International Journal of Applied Pharmaceutics, 11(1), 246–250. https://doi.org/10.22159/ijap.2019.v11s1.19448

Kerru, N., Gummidi, L., Maddila, S., Gangu, K. K., & Jonnalagadda, S. B. (2020). A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules, 25(8). https://doi.org/10.3390/molecules25081909

Liu, L., Huq, S., & Xu, W. (2009). Targeting Cyclooxygenase and Nitric Oxide Pathway Cross-Talk: A New Signal Transduction Pathway for Developing More Effective Anti- Inflammatory Drugs. Current Signal Transduction Therapy, 4(1), 66–75. https://doi.org/10.2174/157436209787048702

Lou, Y., & Zhu, J. (2016). Carboxylic Acid Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals, 221–236. https://doi.org/10.1002/9783527693931.ch16

Mohrig, J. R., Hammond, C. N., & Schatz, P. F. (2010). Technique in Organic Chemistry. In Nature (Vol. 180, Issue 4586). https://doi.org/10.1038/180567a0

Muhi-Eldeen, Z., Finjan, S., Al-Mikhtafi, S., Shehab, M., & Al-Kaissi, E. (2009). Synthesis and anti-inflammatory activities of novel salicylic acid and diflunisal amide derivatives. Jordan Journal of Pharmaceutical Sciences, 2(2), 99–110. Retrieved from https://journals.ju.edu.jo/JJPS/article/view/828/823

Padmini, T., HM, V., Jinendra, U., & B, R. (2021). Synthesis of benzoxazole derivatives by Mannich reaction and invitro cytotoxic, antimicrobial and docking studies. Chemical Data Collections, 31, 100628. https://doi.org/10.1016/j.cdc.2020.100628

Pishawikar, S. A., & More, H. N. (2017). Synthesis, docking and in-vitro screening of mannich bases of thiosemicarbazide for anti-fungal activity. Arabian Journal of Chemistry, 10, S2714–S2722. https://doi.org/10.1016/j.arabjc.2013.10.016

Putri, T. N., Bachtiar, A., & Hayun, H. (2018). Synthesis, Antioxidant, and Anti-inflammatory Activity of Morpholine Mannich base of AMACs ((2E, 6E)-2-((4-hydroxy-3- [morpholin-4-yl-)methyl]phenyl)methylidene)-6-(phenylmethylidene) cyclohexan-1-one) and Its Analogs. Journal of Applied Pharmaceutical Science, 8(5), 19–25. https://doi.org/10.7324/JAPS.2018.8503

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

Rani, V. E., & Ravindranath, L. K. (2016). Synthesis, Characterization and Antimicrobial Evaluation of Novel Mannich Bases Containing Pyrazole-5-One Phosphonates. Open Pharmaceutical Sciences Journal, 3(1), 49–55. https://doi.org/10.2174/1874844901603010049

Razzak, A. Abdul, Nadeem Hussan, F. S., & Qaseer, J. A. (2017). Design and Synthesis of New Non-Steroidal Anti-inflammatory Agents with Expected Selectivity toward Cyclooxygenase-2 Inhibition. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 19(1), 6–13. https://doi.org/10.31351/vol19iss1pp6-13

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). Structural and Chemical Biology of the Interaction of Cyclooxygenase with Substrates and Non-Steroidal Anti-Inflammatory Drugs. Chemical Reviews, 120(15), 7592–7641. https://doi.org/10.1021/acs.chemrev.0c00215

Salahuddin, Hanafi, M., & Hariyanti. (2013). Synthesis and anticancer activity test of 2-hydroxy-N-phenylnicotinamide. Indonesian Journal of Chemistry, 13(2), 166–170. https://doi.org/10.22146/ijc.21300

Sharma, R. K. (2010). Immobilization of Protease And Sorption of BSA on Cellulose, Cellulose Derivatives, And Graft Copolymers. BioResources, 5(4), 2547–2555. Retrieved from shorturl.at/AFLQY

Streppa, H. K., Jones, C. J., & Budsberg, S. C. (2002). Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs in canine blood. American Journal of Veterinary Research, 63(1), 91–94. https://doi.org/10.2460/AJVR.2002.63.91

Suherman, M., Prasetiawati, R., Ramdani, D., Farmasi, P. S., Mipa, F., Garut, U., Jati, J., & Kaler, T. (2020). Virtual Screening Of Tamarind Active Compounds (Tamarindus Indica L.) On Selective Inhibitor Siklooksigenase-2. 125–136. Retrieved from https://journal.uniga.ac.id/index.php/JFB/article/download/879/779

Ugwu, D. I., Okoro, U. C., Ukoha, P. O., Gupta, A., & Okafor, S. N. (2018). Novel anti-inflammatory and analgesic agents: synthesis, molecular docking and in vivo studies. Journal of Enzyme Inhibition and Medicinal Chemistry, 33(1), 405–415. https://doi.org/10.1080/14756366.2018.1426573

Ullah, N., Huang, Z., Sanaee, F., Rodriguez-Dimitrescu, A., Aldawsari, F., Jamali, F., Bhardwaj, A., Islam, N. U., & Velázquez-Martínez, C. A. (2016). NSAIDs do not require the presence of a carboxylic acid to exert their anti-inflammatory effect – why do we keep using it? Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 1018–1028. https://doi.org/10.3109/14756366.2015.1088840

Author Biographies

Gadis Anggraini, universitas indonesia

Hayun Hayun, Universitas Indonesia

Catur Jatmika, University of Indonesia

License

Copyright (c) 2022 gadis anggraini

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with Jurnal Penelitian Pendidikan IPA, agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License (CC-BY License). This license allows authors to use all articles, data sets, graphics, and appendices in data mining applications, search engines, web sites, blogs, and other platforms by providing an appropriate reference. The journal allows the author(s) to hold the copyright without restrictions and will retain publishing rights without restrictions.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Jurnal Penelitian Pendidikan IPA.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).