The Synthesis and Molecular Docking Assay of 2-(3-3,4-dimethoxyphenyl)-6-oxopyridazin-1(6H)-yl)acetohydrazide as a candidate for breast anticancer
DOI:
https://doi.org/10.37859/jp.v16i1.9167
Keywords:
pyridazinone, acetohydrazide, breast cancer, Estrogen alpha
Abstract
Piridazinon merupakan golongan senyawa heterosiklik dengan aktivitas biologis yang luas, salah satunya sebagai antikanker. Penelitian ini mensintesis turunan piridazinon yang disubstitusi N-asetohidrazida dan mengevaluasi potensinya sebagai terapi kanker payudara melalui studi docking molekuler. Senyawa target, 2-(3-(3-metoksifenil)-6-oksopiridazina-1(6H)-il)asetohidrazida (3) , disintesis melalui tiga langkah reaksi: kondensasi untuk membentuk inti piridzinon, fungsionalisasi etil kloroasetat pada posisi nitrogen, dan substitusi gugus etoksi dengan hidrazin hidrat. Rendemen yang diperoleh adalah 48,14%. Kemurnian senyawa yang disintesis dikonfirmasi melalui penentuan titik leleh dan analisis kromatografi cair kinerja tinggi (HPLC), yang menunjukkan satu puncak dominan. Elucidasi struktur menggunakan Fourier-transform infrared (FTIR), spektrometri massa (MS), resonansi magnetik nuklir proton ( 1H -NMR), dan resonansi magnetik nuklir karbon-13 ( 13C -NMR) memverifikasi struktur yang diharapkan. Studi penambatan molekuler terhadap tirosin kinase (PDB ID: 3ERT) menunjukkan bahwa senyawa (3) memiliki energi bebas pengikatan sebesar -7,93 kkal/mol, dengan dua ikatan hidrogen yang terbentuk dengan residu Glu353 dan Leu387. Hasil ini menunjukkan bahwa senyawa (3) belum menunjukkan aktivitas penghambatan yang lebih baik daripada tamoxifen. Meskipun demikian, senyawa ini memenuhi karakteristik fisikokimia yang baik berdasarkan aturan Lipinski, sehingga tetap menjanjikan untuk pengembangan lebih lanjut.
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References
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Xu, J., Meng, Y. Z., Wang, S. J., & Hay, A. S. (2006). Synthesis and characterization of poly(arylene ether)s containing 6-(4-hydroxyphenyl)pyridazin-3(2H)-one or 6-(4-hydroxyphenyl)pyridazine moieties. Journal of Polymer Science, Part A: Polymer Chemistry, 44(10). https://doi.org/10.1002/pola.21441
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Yuliastuti, F., Andayani, T. M., Endarti, D., & Kristina, S. A. (2023). Breast, cervical, and lung cancer: A comparison of real healthcare costs and INA-CBGs rates in the era of national health insurance. Pharmacy Practice, 21(1). https://doi.org/10.18549/PharmPract.2023.1.2768
Bhojwani, H. R., & Joshi, U. J. (2017). Pharmacophore and Docking Guided Virtual Screening Study for Discovery of Type I Inhibitors of VEGFR-2 Kinase. Current Computer-Aided Drug Design. https://doi.org/10.2174/1386207319666161214112536
Casale, M. T., Richman, A. R., Elrod, M. J., Garland, R. M., Beaver, M. R., & Tolbert, M. A. (2007). Kinetics of acid-catalyzed aldol condensation reactions of aliphatic aldehydes. Atmospheric Environment. https://doi.org/10.1016/j.atmosenv.2007.04.002
Chesney, T. R., Yin, J. X., Rajaee, N., Tricco, A. C., Fyles, A. W., Acuna, S. A., & Scheer, A. S. (2017). Tamoxifen with radiotherapy compared with Tamoxifen alone in elderly women with early-stage breast cancer treated with breast conserving surgery: A systematic review and meta-analysis. In Radiotherapy and Oncology. https://doi.org/10.1016/j.radonc.2017.02.019
Clusan, L., Ferrière, F., Flouriot, G., & Pakdel, F. (2023). A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer. In International Journal of Molecular Sciences. https://doi.org/10.3390/ijms24076834
Daoui, S., Direkel, Ş., Ibrahim, M. M., Tüzün, B., Chelfi, T., Al-Ghorbani, M., Bouatia, M., Karbane, M. El, Doukkali, A., Benchat, N., & Karrouchi, K. (2023). Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives. Molecules. https://doi.org/10.3390/molecules28020678
El-Nagar, M. K. S., Shahin, M. I., El-Behairy, M. F., Taher, E. S., El-Badawy, M. F., Sharaky, M., Abou El Ella, D. A., Abouzid, K. A. M., & Adel, M. (2024). Pyridazinone-based derivatives as anticancer agents endowed with anti-microbial activity: molecular design, synthesis, and biological investigation. RSC Medicinal Chemistry, 15, 3529–3557. https://doi.org/10.1039/d4md00481g
Frimayanti, N., Septama, A. W., Teruna, H. Y., & Rahmi, E. P. (2025). In silico investigation of artocarpin, cycloarotcarpin, artocarpanone, and cyanomaclurin for Dengue virus inhibitor DEN2 NS2B/NS3 serine protease. Journal of Pharmacy & Pharmacognosy Research, 13(1), 193–202. https://doi.org/10.56499/jppres24.2052_13.1.193
Gondhowiardjo, S., Christina, N., Ganapati, N. P. D., Hawariy, S., Radityamurti, F., Jayalie, V. F., Octavianus, S., Prawira Putra, A., Sekarutami, S. M., Prajogi, G. B., Giselvania, A., Adham, M., Hamid, A. R. A. H., Widyastuti, E., Prabowo, Y., Aninditha, T., Purwoto, G., Aman, R. A., Siregar, T. P., … Agianda, F. (2021). Five-Year Cancer Epidemiology at the National Referral Hospital: Hospital-Based Cancer Registry Data in Indonesia. JCO Global Oncology, 7. https://doi.org/10.1200/go.20.00155
Ikhtiarudin, I., Dona, R., Frimayanti, N., Utami, R., Susianti, N., & Septama, A. W. (2022). Sintesis, Karakterisasi Struktur, dan Kajian Molecular Docking Senyawa Turunan 4’-Metoksi Flavonol sebagai Antagonis Reseptor Estrogen Alpha (ER-a) pada Kanker Payudara. Jurnal Riset Kimia, 13(2), 236–249. https://doi.org/10.25077/jrk.v13i2.553
Lalu Sanik Wahyu Fadil Amrulloh, Nuraini Harmastuti, Andri Prasetiyo, & Rina Herowati. (2023). Analysis of Molecular Docking and Dynamics Simulation of Mahogany (Swietenia macrophylla King) Compounds Against the PLpro Enzyme SARS-COV-2. Jurnal Farmasi Dan Ilmu Kefarmasian Indonesia, 10(3), 347–359. https://doi.org/10.20473/jfiki.v10i32023.347-359
Malik, A. K., Kumar, R., & Heena. (2015). Spectroscopy: Types. In Encyclopedia of Food and Health (1st ed.). Elsevier Ltd. https://doi.org/10.1016/B978-0-12-384947-2.00643-7
Masand, V. H., Al-Hussain, S. A., Alzahrani, A. Y., Al-Mutairi, A. A., Hussien, R. A., Samad, A., & Zaki, M. E. A. (2024). Estrogen Receptor Alpha Binders for Hormone-Dependent Forms of Breast Cancer: e-QSAR and Molecular Docking Supported by X-ray Resolved Structures. ACS Omega, 9(14), 16759–16774. https://doi.org/10.1021/acsomega.4c00906
Meister, K., Paananen, A., & Bakker, H. J. (2017). Identification of the response of protein N-H vibrations in vibrational sum-frequency generation spectroscopy of aqueous protein films. Physical Chemistry Chemical Physics. https://doi.org/10.1039/c6cp08325k
Merde, İ. B., Önel, G. T., Akkoç, S., Karaköy, Z., & Türkmenoğlu, B. (2023). Focusing on New Piperazinyl-methyl-3(2H)pyridazinone Based Derivatives: Design, Synthesis, Anticancer Activity and Computational Studies. ChemistrySelect, 8(25). https://doi.org/10.1002/slct.202300910
Mirzaei, M., Sheikholeslami, S. A., Jalili, A., Bereimipour, A., Sharbati, S., Kaveh, V., & Salari, S. (2022). Investigating the molecular mechanisms of Tamoxifen on the EMT pathway among patients with breast cancer. Journal of Medicine and Life. https://doi.org/10.25122/jml-2022-0085
Moo, T. A., Sanford, R., Dang, C., & Morrow, M. (2018). Overview of Breast Cancer Therapy. In PET Clinics. https://doi.org/10.1016/j.cpet.2018.02.006
Nandiyanto, A. B. D., Oktiani, R., & Ragadhita, R. (2019). How to read and interpret ftir spectroscope of organic material. Indonesian Journal of Science and Technology. https://doi.org/10.17509/ijost.v4i1.15806
Ong, S. K., Haruyama, R., Yip, C. H., Ngan, T. T., Li, J., Lai, D., Zhang, Y., Yi, S., Shankar, A., Suzanna, E., Jung, S. Y., Ho, P. J., Yusuf, A., Nessa, A., Jung, K. W., Fernando, E., Baral, S., Bagherian, M., Pradhan, P., … Anderson, B. O. (2024). Feasibility of monitoring Global Breast Cancer Initiative Framework key performance indicators in 21 Asian National Cancer Centers Alliance member countries. EClinicalMedicine, 67. https://doi.org/10.1016/j.eclinm.2023.102365
Oskoueian, A., Amin Matori, K., Bayat, S., Oskoueian, E., Ostovan, F., & Toozandehjani, M. (2018). Fabrication, Characterization, and Functionalization of Single-Walled Carbon Nanotube Conjugated with Tamoxifen and Its Anticancer Potential against Human Breast Cancer Cells. Journal of Nanomaterials, 2018. https://doi.org/10.1155/2018/8417016
Qin, J., Zhu, M., Zhu, H., Zhang, L., Fu, Y., Liu, J., Wang, Z., & OuYang, G. (2020). Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety. Phosphorus, Sulfur and Silicon and the Related Elements, 195(7). https://doi.org/10.1080/10426507.2020.1737062
Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L., Kushner, P. J., Agard, D. A., & Greene, G. L. (1998). The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. https://doi.org/10.1016/S0092-8674(00)81717-1
Smith, D. A., Beaumont, K., Maurer, T. S., & Di, L. (2015). Volume of Distribution in Drug Design. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.5b00201
Syahri, J., Hilma, R., Nurlaili, Sari, M. K., Frimayanti, N., Ali, A. H., & Latip, J. (2023). Synthesis, Antimalarial Activities of Secondary Amine-Substituted Eugenol Compounds against Plasmodium falciparum and in silico Molecular Docking Analysis. Sains Malaysiana. https://doi.org/10.17576/jsm-2023-5212-09
Vaidyanathan, R., Murugan Sreedevi, S., Ravichandran, K., Vinod, S. M., Hari Krishnan, Y., Babu, L. K., Parthiban, P. S., Basker, L., Perumal, T., Rajaraman, V., Arumugam, G., Rajendran, K., & Mahalingam, V. (2023). Molecular docking approach on the binding stability of derivatives of phenolic acids (DPAs) with Human Serum Albumin (HSA): Hydrogen-bonding versus hydrophobic interactions or combined influences? JCIS Open. https://doi.org/10.1016/j.jciso.2023.100096
Xu, J., Meng, Y. Z., Wang, S. J., & Hay, A. S. (2006). Synthesis and characterization of poly(arylene ether)s containing 6-(4-hydroxyphenyl)pyridazin-3(2H)-one or 6-(4-hydroxyphenyl)pyridazine moieties. Journal of Polymer Science, Part A: Polymer Chemistry, 44(10). https://doi.org/10.1002/pola.21441
Yan, A., Wang, Z., & Cai, Z. (2008). Prediction of human intestinal absorption by GA feature selection and support vector machine regression. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms9101961
Yuliastuti, F., Andayani, T. M., Endarti, D., & Kristina, S. A. (2023). Breast, cervical, and lung cancer: A comparison of real healthcare costs and INA-CBGs rates in the era of national health insurance. Pharmacy Practice, 21(1). https://doi.org/10.18549/PharmPract.2023.1.2768
Published
2025-11-30
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shalihah, putri, zulmy, winda permata, hendra, rudi, & jasril. (2025). The Synthesis and Molecular Docking Assay of 2-(3-3,4-dimethoxyphenyl)-6-oxopyridazin-1(6H)-yl)acetohydrazide as a candidate for breast anticancer. Photon: Jurnal Sain Dan Kesehatan, 16(1). https://doi.org/10.37859/jp.v16i1.9167
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