Hybridization Synthesis and Anticancer Activity Test of New Carboxylic Acid Derivatives by In-Silico and In-Vitro
DOI:
10.29303/jppipa.v9i9.3439Published:
2023-09-25Downloads
Abstract
Design of new compounds as active ingredients of drugs must be selective and efficient to achieve therapeutic efficacy and minimize resulting side effects. Hybridization synthesis approaches using major components of essential oils can reliably generate new molecules that are superior as active ingredients of anti-cancer drugs due to their cytotoxic properties. This study synthesized a hybrid molecule of citronellyl salicylate by an esterification reaction using Steglich and Fisher method under ultrasonic assistance. The Steglich esterification is more efficient in producing citronellyl salicylate during 30 minutes reaction, yield 12.45%. Analysis of the synthesized product by FTIR is characterized by the presence of typical absorptions of the ester group at ῡ 1650 cm-1 and 1270 cm-1, while LC ESI-MS shows m/z 294 is indicated [M+NH4]+. Anticancer activity was tested in-silico for protein receptors MMP-9, MMP-2, Cyclin-A, p53, and BAK using Molecular Docking Pyrx 9.0 and the highest activity was shown binding affinity value -8.4 kcal/mol for the MMP-9 protein receptor. Similarly, the results of the in vitro activity assay of citronellyl salicylate to 4T1 breast cancer cells showed that the morphology of cancer cells was damaged and the viability of cancer cells was lower than that of normal cells
Keywords:
Anticancer Citronellyl Salicylate Hybridization synthesis Molecular DockingReferences
Ajaykumar, C. (2021). Overview on the Side Effects of Doxorubicin. In Advances in Precision Medicine Oncology. IntechOpen. https://doi.org/10.5772/intechopen.94896
Altun, Ä°., & Sonkaya, A. (2018). The most common side effects experienced by patients were receiving first cycle of chemotherapy. Iranian journal of public health, 47(8), 1218-1219. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123577/
Araújoâ€Filho, H. G. de, dos Santos, J. F., Carvalho, M. T. B., Picot, L., Fruitierâ€Arnaudin, I., Groult, H., Quintansâ€Júnior, L. J., & Quintans, J. S. S. (2021). Anticancer activity of limonene: A systematic review of target signaling pathways. Phytotherapy Research, 35(9), 4957–4970. https://doi.org/10.1002/ptr.7125
A’yun, Q., Warsito, W., & Iftitah, E. D. (2022). Screening the Activity of Limonene and Its Derivatives in Inhibiting the Enzymes MMP-2, MMP-9, and Cyclin A2 in Triple Negative Breast Cancer through Molecular Docking. Jurnal Penelitian Pendidikan IPA, 8(6), 2682–2688. https://doi.org/10.29303/jppipa.v8i6.1917
Cancemi, P., Aiello, A., Accardi, G., Caldarella, R., Candore, G., Caruso, C., Ciaccio, M., Cristaldi, L., Di Gaudio, F., Siino, V., & Vasto, S. (2020). The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs). Mediators of Inflammation, 2020, 1–11. https://doi.org/10.1155/2020/8635158
Crespo-Ortiz, M. P., & Wei, M. Q. (2012). Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug. Journal of Biomedicine and Biotechnology, 2012, 1–18. https://doi.org/10.1155/2012/247597
da Silva, F. F. M., Monte, F. J. Q., de Lemos, T. L. G., do Nascimento, P. G. G., de Medeiros Costa, A. K., & de Paiva, L. M. M. (2018). Eugenol derivatives: Synthesis, characterization, and evaluation of antibacterial and antioxidant activities. Chemistry Central Journal, 12(1), 34. https://doi.org/10.1186/s13065-018-0407-4
Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717. https://doi.org/10.1038/srep42717
Fatmawati, D. R., Hidayat, D. N. W., Sari, D. K., Putri, R. R., Jumina, J., & Kurniawan, Y. S. (2022). Potential of C-Phenylcalix[4]Resorcinarene Epoxide Compound as Drug Delivery Agent in Breast Cancer Cells MCF-7. Jurnal Kimia Sains Dan Aplikasi, 25(3), 123–129. https://doi.org/10.14710/jksa.25.3.123-129
Geiger, T. R., & Peeper, D. S. (2009). Metastasis mechanisms. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1796(2), 293–308. https://doi.org/10.1016/j.bbcan.2009.07.006
Ho, Y., Suphrom, N., Daowtak, K., Potup, P., Thongsri, Y., & Usuwanthim, K. (2020). Anticancer Effect of Citrus hystrix DC. Leaf Extract and Its Bioactive Constituents Citronellol and, Citronellal on the Triple Negative Breast Cancer MDA-MB-231 Cell Line. Pharmaceuticals, 13(12), 476. https://doi.org/10.3390/ph13120476
Jia, S.-S., Xi, G.-P., Zhang, M., Chen, Y.-B., Lei, B., Dong, X.-S., & Yang, Y.-M. (2013). Induction of apoptosis by D-limonene is mediated by inactivation of Akt in LS174T human colon cancer cells. Oncology Reports, 29(1), 349–354. https://doi.org/10.3892/or.2012.2093
Jordan, A., Whymark, K. D., Sydenham, J., & Sneddon, H. F. (2021). A solvent-reagent selection guide for Steglich-type esterification of carboxylic acids. Green Chemistry, 23(17), 6405–6413. https://doi.org/10.1039/D1GC02251B
Karalis, T. T., Chatzopoulos, A., Kondyli, A., Aletras, A. J., Karamanos, N. K., Heldin, P., & Skandalis, S. S. (2020). Salicylate suppresses the oncogenic hyaluronan network in metastatic breast cancer cells. Matrix Biology Plus, 6–7, 100031. https://doi.org/10.1016/j.mbplus.2020.100031
Karthikesh, M. S., & Yang, X. (2021). The effect of ultrasound cavitation on endothelial cells. Experimental Biology and Medicine, 246(7), 758–770. https://doi.org/10.1177/1535370220982301
Lao, J., Madani, J., Puértolas, T., Ãlvarez, M., Hernández, A., Pazo-Cid, R., Artal, Ã., & Antón Torres, A. (2013). Liposomal Doxorubicin in the Treatment of Breast Cancer Patients: A Review. Journal of Drug Delivery, 2013, 1–12. https://doi.org/10.1155/2013/456409
Li, X., Li, X., Liu, F., Li, S., & Shi, D. (2021). Rational Multitargeted Drug Design Strategy from the Perspective of a Medicinal Chemist. Journal of Medicinal Chemistry, 64(15), 10581–10605. https://doi.org/10.1021/acs.jmedchem.1c00683
Ma, H. T., Tsang, Y. H., Marxer, M., & Poon, R. Y. C. (2009). Cyclin A2-Cyclin-Dependent Kinase 2 Cooperates with the PLK1-SCF β-TrCP1 -EMI1-Anaphase-Promoting Complex/Cyclosome Axis To Promote Genome Reduplication in the Absence of Mitosis. Molecular and Cellular Biology, 29(24), 6500–6514. https://doi.org/10.1128/MCB.00669-09
Majhi, S. (2021). Applications of ultrasound in total synthesis of bioactive natural products: A promising green tool. Ultrasonics Sonochemistry, 77, 105665. https://doi.org/10.1016/j.ultsonch.2021.105665
Marei, H. E., Althani, A., Afifi, N., Hasan, A., Caceci, T., Pozzoli, G., Morrione, A., Giordano, A., & Cenciarelli, C. (2021). P53 signaling in cancer progression and therapy. Cancer Cell International, 21(1), 703. https://doi.org/10.1186/s12935-021-02396-8
Oliveira Filho, A. A., Oliveira, H. M. B. F. de, Medeiros, C. I. S., Pessôa, H. de L. F., Siqueira Júnior, J. P. de, & Lima, E. de O. (2017). Antifungal effect of 7-hydroxycitronellal against C. Tropicalis strains: An in vitro approach. Bioscience Journal, 204–208. https://doi.org/10.14393/BJ-v33n1a2017-33851
Panda, S. S., Tran, Q. L., Rajpurohit, P., Pillai, G. G., Thomas, S. J., Bridges, A. E., Capito, J. E., Thangaraju, M., & Lokeshwar, B. L. (2022). Design, Synthesis, and Molecular Docking Studies of Curcumin Hybrid Conjugates as Potential Therapeutics for Breast Cancer. Pharmaceuticals, 15(4), 451. https://doi.org/10.3390/ph15040451
Ramachandran, K., Suganya, T., Nagendra Gandhi, N., & Renganathan, S. (2013). Recent developments for biodiesel production by ultrasonic assist transesterification using different heterogeneous catalyst: A review. Renewable and Sustainable Energy Reviews, 22, 410–418. https://doi.org/10.1016/j.rser.2013.01.057
Steckel, A., & Schlosser, G. (2019). An Organic Chemist’s Guide to Electrospray Mass Spectrometric Structure Elucidation. Molecules, 24(3), 611. https://doi.org/10.3390/molecules24030611
Thuy Giang, L. N., Anh, D. T. T., Phuong, H. T., Thanh, N. H., Giang, N. T. Q., Anh, N. T., Tuyen, N. V., & Kiem, P. V. (2021). DMAP-catalyzed Efficient and Convenient Approach for the Synthesis of 3,3′-(Arylmethylene) bis (2-Hydroxynaphthalene-1,4-Dione) Derivatives. Natural Product Communications, 16(9), 1934578X2110458. https://doi.org/10.1177/1934578X211045808
Webb, A. H., Gao, B. T., Goldsmith, Z. K., Irvine, A. S., Saleh, N., Lee, R. P., Lendermon, J. B., Bheemreddy, R., Zhang, Q., Brennan, R. C., Johnson, D., Steinle, J. J., Wilson, M. W., & Morales-Tirado, V. M. (2017). Inhibition of MMP-2 and MMP-9 decreases cellular migration, and angiogenesis in in vitro models of retinoblastoma. BMC Cancer, 17(1), 434. https://doi.org/10.1186/s12885-017-3418-y
Widiyarti, G., Firdayani, F., Hanafi, M., Kosela, S., & Budianto, E. (2019). Molecular Docking of Citronellol, Geraniol and Ester Derivatives as Pim 1 Kinase Inhibitor of Leukemia Cancer. Jurnal Kimia Valensi, 5(2), 133–142. https://doi.org/10.15408/jkv.v5i2.7195
Widiyarti, G., Megawati, M., & Hanafi, M. (2019). The Potential use of Geraniol Esters from Citronella Oil as Anticancer Agents. Oriental Journal of Chemistry, 35(3), 987–996. https://doi.org/10.13005/ojc/350310
Yeasmin, F., & Choi, H. W. (2020). Natural Salicylates and Their Roles in Human Health. International Journal of Molecular Sciences, 21(23), 9049. https://doi.org/10.3390/ijms21239049
Zari, A. T., Zari, T. A., & Hakeem, K. R. (2021). Anticancer Properties of Eugenol: A Review. Molecules, 26(23), 7407. https://doi.org/10.3390/molecules26237407
License
Copyright (c) 2023 Asyfariatus Zulfa A
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:
- 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.
- 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.
- 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).
