Synthesis and Molecular Docking Study of 4-(3-(2-Chlorophenyl)-5-(2-Methoxyphenyl)-4,5-Dihydro-1H-Pyrazol-1-yl) Benzenesulfonamide as Antibreast Cancer Agent

Eka Marisa Putri, Noval Herfindo, Guntur Guntur, Neni Frimayanti, Adel Zamri

Abstract

Breast cancer is a disease in which cells in the breast tissue change and divide in an uncontrolled way. Pyrazoline is a promising agent reported against cancer. In this work, we have synthesized pyrazoline 4-(3-(2-chlorophenyl)-5-(2-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamide (EMP-1). The reaction was successfully carried out in one-pot three components from 2-chloroacetophenone, 2-methoxybenzaldehyde, and 4-hydrazinylbenzenesulfonamide as starting materials. The reaction was conducted by assisting the irradiation of Monowave 50 (Anton-Paar) with a high yield of 91%. Its potential anti-breast cancer was investigated by molecular docking and dynamic studies. The molecular docking study showed that EMP-1 had binding energy of -7.17 kcal/mol. The spatial arrangement of EMP-1 was similar to the positive control of doxorubicin. These results indicate that EMP-1 compound potentially developed as anti-breast cancer.

Keywords

anticancer; molecular docking; pyrazoline; sulfonamide; tyrosine kinase.

Full Text:

PDF

References

Adamus-Grabicka, A.A., Markowicz-Piasecka, M., Cieślak, M., Królewska-Golińska, K., Hikisz, P., Kusz, J., Małecka, M., and Budzisz, E., 2020. Biological Evaluation of 3-benzylidenechromanones and Their Spiropyrazolines-based Analogues. Molecules, 25(7), 1613. doi: 10.3390/molecules25071613.

Altisen, R. C., Constansa, J. F. C., Bafalluy, R. M., and Rigal, I. C., 2007. Pyrazoline Derivates Useful for the Treatment of Cancer, US 2007/00, 1–12.

American Cancer Society, “Cancer Facts & Figures 2020,” American Cancer Society. 2020, [Online]. Available: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf.

Cuartas, V., Robledo, S.M., Vélez, I.D., Crespo, M.D.P., Sortino, M., Zacchino, S., Nogueras, M., Cobo, J., Upegui, Y., Pineda, T. and Yepes, L., 2020. New Thiazolyl‐Pyrazoline Derivatives Bearing Nitrogen Mustard as Potential Antimicrobial and Antiprotozoal Agents. Archiv der Pharmazie, 353(5), e1900351. doi: 10.1002/ardp.201900351.

Duan, L., Guo, X., Cong, Y., Feng, G., Li, Y., and Zhang, J.Z., 2019. Accelerated Molecular Dynamics Simulation for Helical Proteins Folding in Explicit Water. Frontiers in Chemistry, 7(540), 1–18. doi: 10.3389/fchem.2019.00540.

Frimayanti, N., Yaeghoobi, M., Ikhtiarudin, I., Rizki, D., and Putri, W. 2021. Insight on the In Silico Study and Biological Activity Assay Molecular docking. 20(1), 1–11. doi: 10.12982/CMUJNS.2021.019.

Frimayanti, N., Ikhtiarudin, I., Rahma, D.O.N.A., Agustini, T.T., Murdiya, F., and Zamri, A., 2020. A Computational Approach to Drug Discovery: Search for Chalcone Analogues as the Potential Candidates for Anti-Colorectal Cancer (HT29). Walailak Journal of Science and Technology (WJST), 17(2), 64–74.

Havrylyuk, D., Zimenkovsky, B., Vasylenko, O., and Lesyk, R., 2013. Synthesis and Anticancer and Antiviral Activities of New 2‐Pyrazoline‐Substituted 4‐Thiazolidinones. Journal of Heterocyclic Chemistry, 50(S1), E56–E62. doi: 10.1002/jhet.5570100628.

Herfindo, N., Prasetiawati, R., Sialagan, D., Frimayanti, N., and Zamri, A., 2020. Synthesis, Anti-proliferative Activity and Molecular Docking Studies of 1, 3, 5-triaryl Pyrazole Compound as Estrogen a Receptor Inhibitor Targeting MCF-7 Cells Line. Molekul, 15(1), 18–25. doi: 10.20884/1.jm.2020.15.1.585.

Higa, G.M. and Abraham, J., 2007. Lapatinib in the Treatment of Breast cancer. Expert Review of Anticancer Therapy, 7(9), 1183‒1192. doi: 10.1586/14737140.7.9.1183.

Jasril, J., Ikhtiarudin, I., Hasti, S., Indah, A.I., and Frimayanti, N., 2019. Microwave-Assisted Synthesis, in Silico Studies and in vivo Evaluation for the Antidiabetic Activity of New Brominated Pyrazoline Analogs. Thai Journal of Pharmaceutical Sciences, 43(2), 83‒89.

Jasril, J., Zamri, A., Ikhtiarudin, I. and Teruna, H.Y., 2016. 5-(4-Fluorophenyl)-3-(naphthalen-1-yl)-1-Phenyl-4, 5-dihydro-1H-pyrazole. Molbank, 2016(2), 1-5. doi: 10.3390/M891.

Ji-Tai, L., Xiao-Hui, Z., and Zhi-Ping, L., 2007. An Improved Synthesis of 1, 3, 5-Triaryl-2-Pyrazolines in Acetic Acid Aqueous Solution. Beilstein J ournal Organic Chemistry, 3, 1‒4. doi: 10.1186/1860-5397-3-13.

Meric-Bernstam, F. and Hung, M.C., 2006. Advances in Targeting Human Epidermal Growth Factor Receptor-2 Signaling for Cancer Therapy. Clinical Cancer Research, 12(21), 6326‒6330. doi: 10.1158/1078-0432.CCR-06-1732.

Ozawa, Y., Kusano, K., Owa, T., Yokoi, A., Asada, M., and Yoshimatsu, K., 2012. Therapeutic Potential and Molecular Mechanism of a Novel Sulfonamide Anticancer Drug, Indisulam (E7070) in Combination with CPT-11 for Cancer Treatment. Cancer Chemotherapy and Pharmacology, 69(5), 1353‒1362. doi: 10.1007/s00280-012-1844-8.

Piccart-Gebhart, M.J., Procter, M., Leyland-Jones, B., Goldhirsch, A., Untch, M., Smith, I., Gianni, L., Baselga, J., Bell, R., Jackisch, C., and Cameron, D., 2005. Trastuzumab After Adjuvant Chemotherapy in HER2-Positive Breast Cancer. New England Journal of Medicine, 353(16), 1659‒1672. doi: 10.1056/NEJMoa052306.

Soliman, R., 1979. Preparation and Antidiabetic Activity of Some Sulfonylurea Derivatives Of 3, 5-Disubstituted Pyrazoles. Journal of Medicinal Chemistry, 22(3), 321‒325. doi: 10.1021/jm00189a022.

Teruna, H.Y., Aisyah, A., Nurlaili, N., and Hendra, R., 2019. Microwave Assisted Synthesis and Evaluation of Toxicity and Antioxidant Activity of Pyrazoline Derivatives. Indonesian Journal of Chemistry, 19, 583‒91. doi: 10.22146/ijc.34285.

Varghese, B., Al-Busafi, S.N., Suliman, F.O., and Al-Kindy, S.M., 2017. Unveiling A Versatile Heterocycle: Pyrazoline–A Review. RSC Advances, 7(74), 46999−47016. doi: 10.1039/C7RA08939B.

World Health Organization, “Latest Global Cancer Data: Cancer Burden Rises to 18.1 Million New Cases and 9.6 Million Cancer Deaths in 2018,” International Agency for Research on Cancer, pp. 1–3, 2018, [Online]. Available: https://www.who.int/cancer/PRGlobocanFinal.pdf.

Zamri, A., Teruna, H.Y., Wulansari, S., Herfindo, N., Frimayanti, N. and Ikhtiarudin, I., 2019. 3-(3, 4-Dimethoxyphenyl)-5-(2-fluorophenyl)-1-phenyl-4, 5-dihydro-1H-pyrazole. Molbank, 2019(4),1-8. doi: 10.3390/M1088.

DOI: https://doi.org/10.20961/alchemy.18.1.48298.30-36

Refbacks

  • There are currently no refbacks.