Synthesis, Characterization and Molecular Docking of New Naphthalene-Based Chalcone and Pyrazoline Compounds

Abstract:

Most chemotherapeutic drugs are unable to distinguish between healthy and cancerous cells, resulting in the risk of side effects and drug resistance. There is a continuous effort to find new agents to help bring this disease under control. Compounds with bioactive natural product scaffolds have been of great interest due to their low toxicity and high efficacy. In this study, new naphthalene-based chalcone 1 and pyrazoline 1A compounds were synthesized via a Claisen-Schmidt condensation and cyclo-condensation reaction, respectively. These compounds were characterized using the Fourier Transform Infrared (FT-IR), ¹H, and ¹³C Nuclear Magnetic Resonance (NMR) spectroscopy. The molecular docking activities were performed to study the interactions between these new compounds with breast cancer protein, 3ERT as estrogen receptor-α (ERα). Chalcone 1 and pyrazoline 1A compounds obey Lipinski's rule whereby pyrazoline 1A showed the lowest binding energy of -9.47 kcal/mol, inhibition constant of 113.93 mM and log P of 2.30. Interaction of pyrazoline 1A with 3ERT protein exhibited the hydrogen bonding with GLY521 amino acid, while the hydrophobic interactions were observed with LEU346, LEU384, LEU391, LEU525, LEU387, MET343, ALA350, and MET421 amino acids. Pyrazoline 1A is expected to show promising activities as an anticancer agent.

• Periodical: Materials Science Forum (Volume 1068)
• Pages: 167-174
• DOI: https://doi.org/10.4028/p-kt55yh
• Online since: August 2022
• Authors: Taki Eddine Othmani, Mohammad Murwih Alidmat, Melati Khairuddean*, Tutik Dwi Wahyuningsih
• Keywords: Chalcone, Molecular Docking, Naphthalene, Pyrazine, Pyrazoline

References

[1] J.T. de Giffoni de Carvalho, D. da Silva Baldivia, D.F. Leite, L.C.A. de Araújo, P.P. de Toledo Espindola, K.A. Antunes, P.S. Rocha, K. Dos Santos, E.L. de Picoli Souza, Medicinal plants from Brazilian cerrado: Antioxidant and anticancer potential and protection against chemotherapy toxicity, Oxid. Med. Cell. Longev. (2019) 1-16.

DOI: 10.1155/2019/3685264

[2] D. Elkhalifa, A.B. Siddique, M. Qusa, F.S. Cyprian, K. El Sayed, F. Alali, A.-E. Al Moustafa, A. Khalil, Design, synthesis, and validation of novel nitrogen-based chalcone analogs against triple-negative breast cancer, Eur. J. Med. Chem. 187 (2020) 111954.

DOI: 10.1016/j.ejmech.2019.111954

[3] D.A. Dindar, G. Albayrak, A. Ozet, The importance of cancer stem cells in gastrointestinal cancers, Crit. Rev. Oncog. 24, 1 (2019) 55-59.

DOI: 10.1615/critrevoncog.2018029633

[4] P. Singh, A. Kumar, V. Anand, Recent developments in biological activities of chalcones: a mini review, Eur. J. Med. Chem. 85 (2014) 758-777.

DOI: 10.1016/j.ejmech.2014.08.033

[5] S. Sapra, K. Sharma, Y. Dhar, K. Bhalla, Chalconoid derived heterocycles as potent bioactive molecules: a review, Chem. Sci. J. 7 (2016) 1000129.

[6] C. Zhuang, W. Zhang, C. Sheng, W. Zhang, C. Xing, Z. Miao, Chalcone: a privileged structure in medicinal chemistry, Chem. Rev. 117, 12 (2017) 7762-7810.

DOI: 10.1021/acs.chemrev.7b00020

[7] Z. Hosseinzadeh, A. Ramazani, N. Razzaghi-Asl, Anti-cancer nitrogen-containing heterocyclic compounds, Curr. Org. Chem. 22, 23 (2018) 2256-2279.

DOI: 10.2174/1385272822666181008142138

[8] N. Kerru, L. Gummidi, S. Maddila, K.K. Gangu, S.B. Jonnalagadda, A review on recent advances in nitrogen-containing molecules and their biological applications, Molecules, 25, 8 (2020) (1909).

DOI: 10.3390/molecules25081909

[9] H. Irannejad, Nitrogen-rich heterocycles as a privileged fragment in lead discovery, Med. Anal. Chem. Int. J. 2 (2018) 1-6.

DOI: 10.23880/macij-16000125

[10] B. Sever, M.D. Altıntop, H.K. Gencer, H.A. Kapkac, O. Atli, M. Baysal, A. Ozdemir, Synthesis of new thiazolyl-pyrazoline derivatives and evaluation of their antimicrobial, cytotoxic and genotoxic effects, Lett. Drug Des. Discov. 15, 7 (2018) 744-756.

DOI: 10.2174/1570180814666170925152902

[11] V. Abbot, P. Sharma, S. Dhiman, M.N. Noolvi, H.M. Patel, V. Bhardwaj, Small hybrid heteroaromatics: resourceful biological tools in cancer research, RSC Adv. 7 (2017) 28313.

DOI: 10.1039/c6ra24662a

[12] M. de Oliveira Pedrosa, J. de Oliveira Viana, R.O. Moura, R.M.D. da Cruz, Hybrid compounds as direct multitarget ligands: A review, Curr. Top. Med. Chem. 16, 999 (2016) 1.

DOI: 10.2174/1568026616666160927160620

[13] X.-Y. Meng, H.-X. Zhang, M. Mezei, M. Cui, Molecular docking: a powerful approach for structure-based drug discovery, Curr. Comput. Aided Drug Des. 7, 2 (2011) 146-157.

DOI: 10.2174/157340911795677602

[14] R.F. de Freitas, M. Schapira, A systematic analysis of atomic protein–ligand interactions in the PDB, Med. Chem. Comm. 8, 10 (2017) 1970-1981.

DOI: 10.1039/c7md00381a

[15] A.M. Dar, S. Mir, Molecular docking: approaches, types, applications and basic challenges, J. Anal. Bioanal. Tech. 8, 2 (2017) 1-3.

DOI: 10.4172/2155-9872.1000356

[16] X. Du, Y. Li, Y.-L. Xia, S.-M. Ai, J. Liang, P. Sang, X.-L. Ji, S.-Q. Liu, Insights into protein–ligand interactions: mechanisms, models, and methods, Int. J. Mol. Sci. 17, 2 (2016) 144.

DOI: 10.3390/ijms17020144

[17] H. Hua, H. Zhang, Q. Kong, Y. Jiang, Mechanisms for estrogen receptor expression in human cancer, Exp. Hematol. Oncol. 7, 1 (2018) 1-11.

DOI: 10.1186/s40164-018-0116-7

[18] M. Livezey, J.E. Kim, D.J. Shapiro, A new role for estrogen receptor α in cell proliferation and cancer: Activating the anticipatory unfolded protein response. Front. Endocrinol. 9 (2018) 325.

DOI: 10.3389/fendo.2018.00325

[19] M. Chang, Tamoxifen resistance in breast cancer, Biomol Ther (Seoul). 20, 3 (2012) 256-267.

[20] C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev. 64 (2012) 4-17.

DOI: 10.1016/j.addr.2012.09.019

[21] Y.K. Bosken, T. Cholko, Y.-C. Lou, K.-P. Wu, C.-E.A. Chang, Insights into dynamics of inhibitor and ubiquitin-like protein binding in SARS-CoV-2 papain-like protease, Front. Mol. Biosci. 7 (2020) 174.

DOI: 10.3389/fmolb.2020.00174

[22] J. Shawon, A. Mahmud Khan, I. Shahriar, M.A. Halim, Improving the binding affinity and interaction of 5-pentyl-2-phenoxyphenol against Mycobacterium enoyl ACP reductase by computational approach, Inform. Med. Unlocked. 23 (2021) 100528.

DOI: 10.1016/j.imu.2021.100528