Design, synthesis, characterization, and cytotoxicity activity evaluation of mono-chalcones and new pyrazolines derivatives

Kassim Ali Salum; Mohammad Murwih Alidmat; Melati Khairulddean; Nik Nur Syazni Nik Mohammad Kamal; Musthahimah Muhammad

doi:10.7324/JAPS.2020.10803

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Abstract

The development of resistance and side effects of chemotherapeutic drugs are common obstacles in the treatment of cancer. With the expansion of health problems nowadays, there is a need to continuously develop new drugs that are more efficient in targeting tumor cells and safe to normal cells. This study designed a series of new chalcones and pyrazoline derivatives based on their binding energy from the molecular docking study. The synthesis involved Claisen–Schmidt condensation to form two chalcones, 1 and 2, which are then cyclized at room temperature to form eight new pyrazoline derivatives, 3–10. A one-pot reaction of acetophenone, 2-ethoxybenzaldehyde, and hydrazide derivatives (thiosemicarbazide and phenyl hydrazide) under reflux formed two new pyrazoline derivatives, 11 and 12, without the isolation of chalcones. All the synthesized chalcones and pyrazolines were characterized using the Fourier transform infrared spectroscopy–attenuated total reflectance and nuclear magnetic resonance (1D and 2D). The cytotoxicity activity of the chalcones and new pyrazoline compounds were investigated against breast cancer cell lines (MCF-7 and MD-MB-231) and normal breast cell lines (MCF-10A). The results show that only compound 7 showed the minimum inhibition against MCF-7 with IC₅₀6.50 μM when exposed to the cell line for 24 hours compared to the reference Gefitinib anticancer drug.

Keyword: Chalcone pyrazoline claisen–schmidt condensation acetophenone.

Citation:

Salum KA, Murwih M, Khairuddean M, Kamal NNSNM, Muhammad M. Design, synthesis, characterization, and cytotoxicity activity evaluation of mono-chalcones and new pyrazolines derivatives. J Appl Pharm Sci, 2020; 10(08):020-036.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

Akram M, Siddiqui S. Breast cancer management: past, present and evolving. Indian J Cancer, 2012; 49(3):277. https://doi.org/10.4103/0019-509X.104486
Aksöz BE, Ertan R. Chemical and structural properties of chalcones I. FABAD J Pharm Sci, 2011; 36:223-42.
Alkorta I, Elguero J. The tautomerism of pyrazolines (dihydropyrazoles). J Chil Chem Soc, 2015; 60(2):2966-70. https://doi.org/10.4067/S0717-97072015000200022
Arora P, Arora V, Lamba H, Wadhwa D. Importance of heterocyclic chemistry: a review. Int J Pharm Sci Res, 2012; 3(9):2947.
Arruebo M, Vilaboa N, Sáez-Gutierrez B, Lambea J, Tres A, Valladares M, González-Fernández Á. Assessment of the evolution of cancer treatment therapies. Cancers, 2011; 3(3):3279-330. https://doi.org/10.3390/cancers3033279
Hassan MRA, Ismail I, Suan MAM, Ahmad F, Khazim WKW, Othman, Z, Mohammed NS. Incidence and mortality rates of colorectal cancer in Malaysia. Epidemiol Health, 2016; 38:e2016007. https://doi.org/10.4178/epih.e2016007
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin, 2011; 61(2):69-90. https://doi.org/10.3322/caac.20107
Kumar C, Loh WS, Ooi C, Quah C, Fun HK. Structural correlation of some heterocyclic chalcone analogues and evaluation of their antioxidant potential. Molecules, 2013; 18(10):11996-2011. https://doi.org/10.3390/molecules181011996
Liu Y, El-Ashry D, Chen D, Ding I, Kern F. Emergence of MCF-7 cells over-expressing a transfected epidermal growth factor receptor (EGFR) under estrogen-depleted conditions: evidence for a role of EGFR in breast cancer growth and progression. Cell Growth Differ, 1994; 5:1263-74.
Manupati K, Dhoke NR, Debnath T, Yeeravalli R, Guguloth K, Saeidpour S, Das A. Inhibiting epidermal growth factor receptor signalling potentiates mesenchymal-epithelial transition of breast cancer stem cells and their responsiveness to anticancer drugs. FEBS J, 2017; 284(12):1830-54. https://doi.org/10.1111/febs.14084
Mazumdar M, Fournier D, Zhu DW, Cadot C, Poirier D, Lin SX. Binary and ternary crystal structure analyses of a novel inhibitor with 17β-HSD type 1: a lead compound for breast cancer therapy. Biochem J, 2009; 424(3):357-66. https://doi.org/10.1042/BJ20091020
Moerkens M, Zhang Y, Wester L, van de Water B, Meerman JH. Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation. BMC Cancer, 2014; 14(1):283. https://doi.org/10.1186/1471-2407-14-283
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem, 2009; 30(16):2785-91. https://doi.org/10.1002/jcc.21256
Prashar H, Chawla A, Sharma AK, Kharb R. Chalcone as a versatile moiety for diverse pharmacological activities. Int J Pharm Sci Res, 2012; 3(7):1913.
Puja Jaiswal DPP, Himangini B, Uma A. Chalcone and their heterocyclic analogue: a review article. J Chem Pharm Res, 2018; 10(4):160-173.
Saini R. K, Chouhan R, Bagri L. P, Bajpai A. Strategies of targeting tumors and cancers. Journal of Cancer Research Updates,2012; 1(1):173-179.
Shaik NA, Al-Kreathy HM, Ajabnoor GM, Verma PK, Banaganapalli B. Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR. Saudi J Biol Sci, 2019; 26(3):439-48. https://doi.org/10.1016/j.sjbs.2018.05.026
Shaikh AR, Farooqui M, Satpute R, Abed S. Overview on nitrogen containing compounds and their assessment based on 'International Regulatory Standards'. J Drug Deliv Ther, 2018; 8(6-s):424-8. https://doi.org/10.22270/jddt.v8i6-s.2156
Sharma GN, Dave R, Sanadya J, Sharma P, Sharma K. Various types and management of breast cancer: an overview. J Adv Pharm Technol Res, 2010; 1(2):109.
Skrzydlewska E, Sulkowski S, Koda M, Zalewski B, Kanczuga- Koda L, Sulkowska M. Lipid peroxidation and antioxidant status in colorectal cancer. World J Gastroenterol, 2005; 11(3):403. https://doi.org/10.3748/wjg.v11.i3.403
WHO. 2019. Breast cancer[ONLINE] Available via https:// www.who.int/cancer/prevention/diagnosis-screening/breast-cancer/en/ (Accessed 30 November 2019)
Wishart DSFY, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. Gefitinib, DrugBank 5.0. Nucleic Acids Res. 2019. [ONLINE] Available via https://www.drugbank.ca/drugs/DB00317 (Accessed 28 November 2019).
Zayed M, Ahmed S, Ihmaid S, Ahmed H, Rateb H, Ibrahim S. Design, synthesis, cytotoxic evaluation and molecular docking of new fluoroquinazolinones as potent anticancer agents with dual EGFR kinase and tubulin polymerization inhibitory effects. Int J Mol Sci, 2018; 19(6):1731. https://doi.org/10.3390/ijms19061731
Zayed MF, Ahmed HE, Ihmaid S, Omar ASM, Abdelrahim AS. Synthesis and screening of some new fluorinated quinazolinone-sulphonamide hybrids as anticancer agents. J Taibah Univ Med Sci, 2015; 10(3):333-9. https://doi.org/10.1016/j.jtumed.2015.02.007

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