STUDI IN SILICO POTENSI AKTIVITAS FARMAKOLOGI SENYAWA GOLONGAN DIHIDROTETRAZOLOPIRIMIDIN

  • N. Kurnyawaty Jurusan Teknik Kimia, Politeknik Negeri Samarinda, Samarinda, Indonesia
  • H. Suwito Departemen Kimia, Fakultas Sains dan Teknologi, Universitas Airlangga, Surabaya, Indonesia
  • F. Kusumattaqiin Jurusan Teknik Kimia, Politeknik Negeri Samarinda, Samarinda, Indonesia

Abstract

Senyawa golongan dihidrotetrazolopirimidin dapat disintesis menggunakan Reaksi Biginelli. Senyawa etil 5-metil-7-(4-morfolinofenil)-4,7-dihidrotetrazolo[1,5a] pirimidin-6-karboksilat (MDP) merupakan senyawa organik baru terdiri atas cincin dihidrotetrazolopirimidin dengan gugus samping morfolinofenil. Penelitian sebelumnya menyebutkan bahwa senyawa pirimidin dan turunannya memiliki berbagai macam aktivitas farmakologi. Pada penelitian ini, senyawa MDP dianalisis menggunakan studi in silico untuk mengetahui potensi yang dimiliki sebagai agen terapi untuk mengatasi masalah kesehatan. Hasil analisis menunjukkan bahwa senyawa MDP berpotensi sebagai antimalaria, antikanker, dan antihiperurisemia dilihat dari binding energy yang bernilai negatif atau rendah. Interaksi senyawa MDP dengan reseptor yang bernilai paling negatif pada saat berinteraksi dengan protein XOD dibandingkan dengan nilai binding energy MDP dengan Kinesin Eg5 dan PfDHODH. Sehingga dapat disimpulkan bahwa senyawa MDP paling potensial jika digunakan sebagai antihiperurisemia dengan nilai binding energy sebesar -8,33 kkal/mol dengan konstanta inhibisi 0,79 µM.


Kata kunci:   antihiperurisemia, antikanker, antimalaria,  dihidrotetrazolopirimidin, in silico


Dihydrotetrazolopyrimidine derivatives can be synthezed using the Biginelli Reaction. Ethyl 5-methyl-7-(4-morpholinophenyl)-4,7-dihydrotetrazolo[1,5a]pyrimidine-6-carboxylate (MDP) is a new organic compound consisting of a dihydrotetrazolopyrimidine ring with morpholinophenyl moiety. Previous studies showed that pyrimidine compounds and their derivatives exhibited various pharmacological activities. In this study, MDP compound was analyzed using in silico studies to determine its potential to be used as therapeutic agent to overcome health problems. The results of the analysis showed that the MDP compound has potential activity as an antimalarial, anticancer, and antihyperuricemia, based on negative or low binding energy. The interaction of MDP compound with XOD protein showed the lowest binding energy compared to Kinesin Eg5 and PfDHODH. Based on the docking experiments performed, it can be concluded that MDP compound showed the most potential to be used as an antihyperuricemia with binding energy of -8.33 kcal/mol and inhibition concentration of 0,79 µM.


Keywords: anticancer, antihyperuricemia, antimalarial, dihydrotetrazolopyrimidine, in silico

Downloads

Download data is not yet available.

References

Castro-Alvarez, A., Costa, A. M., & Vilarrasa, J. 2017. The Performance of several docking programs at reproducing protein-macrolide-like crystal structures. Molecules. 22(1): 136.
Deng, X., Gujjar, R., El Mazouni, F., Kaminsky, W., Malmquist, N. A., Goldsmith, E. J., Rathod, P. K., & Phillips, M. A. 2009. Structural plasticity of malaria dihydroorotate dehydrogenase allows selective binding of diverse chemical scaffolds. J. Biol. Chem. 284(39): 26999–27009.
Guido, B. C., Ramos, L. M., Nolasco, D. O., Nobrega, C. C., Andrade, B. Y., Pic-Taylor, A., Neto, B. A., & Corrêa, J. R. 2015. Impact of kinesin Eg5 inhibition by 3,4-dihydropyrimidin-2(1H)-one derivatives on various breast cancer cell features. BMC Cancer. 15(1): 283.
Hou, X., Chen, X., Zhang, M., & Yan, A. 2016. QSAR study on the antimalarial activity of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. SAR QSAR Environ. Res. 27(2): 101–124.
Kamal, A., Dastagiri, D., Janaki Ramaiah, M., Surendranadha Reddy, J., Vijaya Bharathi, E., Kashi Reddy, M., Victor Prem Sagar, M., Lakshminarayan Reddy, T., Pushpavalli, S. N. C. V. L., & Pal-Bhadra, M. 2011. Synthesis and apoptosis inducing ability of new anilino substituted pyrimidine sulfonamides as potential anticancer agents. Eur. J. Med. Chem. 46(12): 5817–5824.
Maiuolo, J., Oppedisano, F., Gratteri, S., Muscoli, C., & Mollace, V. 2016. Regulation of uric acid metabolism and excretion. Int. J. Cardiol. 213: 8–14.
Meng, X.-Y., Zhang, H.-X., Mezei, M., & Cui, M. 2012. Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery. Current Computer Aided-Drug Design. 7(2): 146–157.
Okamoto, K., Eger, B. T., Nishino, T., Pai, E. F., & Nishino, T. 2008. Mechanism of inhibition of xanthine oxidoreductase by allopurinol: Crystal structure of reduced bovine milk xanthine oxidoreductase bound with oxipurinol. Nucleosides, Nucleotides and Nucleic Acids. 27(6–7): 888–893.
Rath, O., & Kozielski, F. 2012. Kinesins and cancer. Nature Reviews Cancer. 12(8): 527–539.
Scapin, E., Frizzo, C. P., Rodrigues, L. V., Zimmer, G. C., Vaucher, R. A., Sagrillo, M. R., Giongo, J. L., Afonso, C. A. M., Rijo, P., Zanatta, N., Bonacorso, H. G., & Martins, M. A. P. 2017. Synthesis, antimicrobial activity and cytotoxic investigation of novel trifluoromethylated tetrazolo[1,5-a]pyrimidines. Medicinal Chemistry Research. 26(3): 640–649.
Singh, A., Maqbool, M., Mobashir, M., & Hoda, N. 2017. Dihydroorotate dehydrogenase: A drug target for the development of antimalarials. Eur. J. Med. Chem. 125: 640–651.
Suwito, H., Kurnyawaty, N., Ul Haq, K., Abdulloh, A., & Indriani, I. 2018. Ethyl 5-methyl-7-(4-morpholinophenyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate. Molbank. (2): M998.
Wu, L., Liu, Y., & Li, Y. 2018. Synthesis of spirooxindole-O-naphthoquinone-tetrazolo[1,5-a] pyrimidine hybrids as potential anticancer agents. Molecules. 23(9): 1–9.
Yan, Y., Sardana, V., Xu, B., Homnick, C., Halczenko, W., Buser, C. A., Schaber, M., Hartman, G. D., Huber, H. E., & Kuo, L. C. 2004. Inhibition of a Mitotic Motor Protein: Where, How, and Conformational Consequences. J. Mol. Biol. 335(2): 547–554.
Yerragunta, V., Patil, P., Anusha, V., Kumaraswamy, T., Suman, D., & Samhitha, T. 2013. Pyrimidine and Its Biological Activity: A Review. Pharma Tutor. 1(2): 39–44.
Yuriev, E., & Ramsland, P. A. 2013. Latest developments in molecular docking: 2010-2011 in review. J. Mol. Recognit. 26(5): 215–239.
Published
2021-07-31
How to Cite
KURNYAWATY, N.; SUWITO, H.; KUSUMATTAQIIN, F.. STUDI IN SILICO POTENSI AKTIVITAS FARMAKOLOGI SENYAWA GOLONGAN DIHIDROTETRAZOLOPIRIMIDIN. Jurnal Kimia (Journal of Chemistry), [S.l.], p. 172-179, july 2021. ISSN 2599-2740. Available at: <https://ojs.unud.ac.id/index.php/jchem/article/view/60901>. Date accessed: 05 oct. 2022. doi: https://doi.org/10.24843/JCHEM.2021.v15.i02.p07.
Section
Articles