synthesis of novel carbazole chalcones - pyrazoline derivatives and study of their potential cytotoxicity to colon, lung and breast cancer
DOI:
https://doi.org/10.54153/sjpas.2025.v7i2.946Keywords:
chalcones, carbazole, pyrazoline, anti-cancer colonAbstract
Novel chalcones containing a carbazole ring were prepared through the condensation process between 9-ethyl-3-carbazolecarboxaldehyde and 2-acetyl-5-bromothiophene and 3-acetyl-2,5-dimethyl thiophene by the Claisen-Schmidt method. The chalcones are highly effective against cancer cells, so three types of cancers were used, A-549 lung cancer, MCF-7 breast cancer, and HCT-116 colon cancer: Lung cancer, MCF-7: Breast cancer, Adenocarcinoma and HCT-116: Colorectal cancer, where we observed that chalcones are very effective against colon cancer cells and IC-50 was equal to 4. 5 μM for compound La, while compound Lb had an IC-50 of 0. 9 μM, and derivatives of chalcones, which are heterocyclic pyrazoline rings, were also synthesised using hydrazine and its derivatives, these compounds are also effective against cancer cells, and a comparison was carried out between chalcones and derivatives of these rings and it was found that chalcones are more effective against colon cancer cells, where the IC-50 of compound La1 was 66.5 μM and compound Lb3 was 27.6 μM, the IC-50 of compound La1 was equal to 66.5 μM.
References
1. Naik, V.S., Jayanna, H.S., Vinitha, G.: Synthesis, molecule growth, characterization, theoretical studies and nonlinear optical properties of new chalcone derivative containing thiophene moiety for optical device applications. Indian J. Phys. 95, 1517–1531 (2021). https://doi.org/10.1007/s12648-020-01803-6
2. Ravindra, H.J., Chandrashekaran, K., Harrison, W.T.A., Dharmaprakash, S.M.: Structure and NLO property relationship in a novel chalcone co-crystal. Appl. Phys. B. 94, 503–511 (2009)
3. D’silva, E.D., Rao, D.N., Philip, R., Butcher, R.J., Dharmaprakash, S.M.: Synthesis, growth and characterization of novel second harmonic nonlinear chalcone crystal. J. Phys. Chem. Solids. 72, 824–830 (2011)
4. Kamal, A., Kashi Reddy, M., Viswanath, A.: The design and development of imidazothiazole-chalcone derivatives as potential anticancer drugs. Expert Opin. Drug Discov. 8, 289–304 (2013). https://doi.org/10.1517/17460441.2013.758630
5. Dhahi, L.A.: Synthesis and Characterization of new Schiff base Derived from Benzothiazole with (Salicyldehyde and Saccharin) and Complexes for some Metal Ions (Co, Ni, Cd and Hg). J. Glob. Pharma Technol. 10, 232–241 (2018)
6. Farooq, S., Ngaini, Z.: Recent synthetic methodologies for chalcone synthesis (2013-2018). Curr. Organocatalysis. 6, 184–192 (2019)
7. Ii, N.T., Inhibitors, C., Inducers, A.: Synthesis of Carbazole Derivatives Containing Chalcone Analogs as. 1–49
8. Modzelewska, A., Pettit, C., Achanta, G., Davidson, N.E., Huang, P., Khan, S.R.: Anticancer activities of novel chalcone and bis-chalcone derivatives. Bioorg. Med. Chem. 14, 3491–3495 (2006)
9. Sengul, I.F., Okutan, E., Kandemir, H., Astarci, E., Çoşut, B.: Carbazole substituted BODIPY dyes: Synthesis, photophysical properties and antitumor activity. Dye. Pigment. 123, 32–38 (2015). https://doi.org/10.1016/j.dyepig.2015.07.025
10. Bhatthula, B. kumar goud, Kanchani, J. reddy, Arava, V. reddy, Subha, M.C.S.: Total synthesis of carbazole alkaloids. Tetrahedron. 75, 874–887 (2019). https://doi.org/10.1016/j.tet.2019.01.003
11. Nelson, G., Alam, M.A., Atkinson, T., Gurrapu, S., Sravan Kumar, J., Bicknese, C., Johnson, J.L., Williams, M.: Synthesis and evaluation of p-N,N-dialkyl substituted chalcones as anti-cancer agents. Med. Chem. Res. 22, 4610–4614 (2013). https://doi.org/10.1007/s00044-013-0469-8
12. Xu, N., Zhang, Q., Zhang, G.: A carbazole-functionalized metal-organic framework for efficient detection of antibiotics, pesticides and nitroaromatic compounds. Dalt. Trans. 48, 2683–2691 (2019). https://doi.org/10.1039/c8dt04558e
13. Caruso, A., Ceramella, J., Iacopetta, D., Saturnino, C., Mauro, M.V., Bruno, R., Aquaro, S., Sinicropi, M.S.: Gk_65. Molecules. 24, (2019)
14. Asche, C., Demeunynck, M.: Antitumor carbazoles. Anti-Cancer Agents Med. Chem. (Formerly Curr. Med. Chem. Agents). 7, 247–267 (2007)
15. Vlaar, C.P., Castillo-Pichardo, L., Medina, J.I., Marrero-Serra, C.M., Vélez, E., Ramos, Z., Hernández, E.: Design, synthesis and biological evaluation of new carbazole derivatives as anti-cancer and anti-migratory agents. Bioorganic Med. Chem. 26, 884–890 (2018). https://doi.org/10.1016/j.bmc.2018.01.003
16. Bandgar, B.P., Adsul, L.K., Chavan, H. V, Jalde, S.S., Shringare, S.N., Shaikh, R., Meshram, R.J., Gacche, R.N., Masand, V.: Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents. Bioorg. Med. Chem. Lett. 22, 5839–5844 (2012)
17. Salum, K.A., Alidmat, M.M., Khairulddean, M., Kamal, N.N.S.N.M., Muhammad, M.: Design, synthesis, characterization, and cytotoxicity activity evaluation of mono-chalcones and new pyrazolines derivatives. J. Appl. Pharm. Sci. 10, 20–36 (2020). https://doi.org/10.7324/JAPS.2020.10803
18. Chouiter, M.I., Boulebd, H., Pereira, D.M., Valentão, P., Andrade, P.B., Belfaitah, A., Silva, A.M.S.: New chalcone-type compounds and 2-pyrazoline derivatives: Synthesis and caspase-dependent anticancer activity. Future Med. Chem. 12, 493–509 (2020). https://doi.org/10.4155/fmc-2019-0342
19. Slaihim, M.M., Dhahi, L.A., Ali, A.H.: Innovative Piperidine-Catalyzation in Protecting Carbonyl Compounds with Implications for Angiogenesis and Inflammation. J. Angiother. 8, (2024). https://doi.org/10.25163/angiotherapy.819343
20. Kaka, K.N., Taher, S.G., Hamad, W.M., Ibrahim, A.H.: Synthesis of new series of Pyrazoline, and study their Kinetics and Reaction Mechanism. Aro-the Sci. J. Koya Univ. 7, 5–13 (2019). https://doi.org/10.14500/aro.10508
21. Bonakdar, A.P.S., Sadeghi, A., Aghaei, H.R., Beheshtimaal, K., Nazifi, S.M.R., Massah, A.R.: Convenient Synthesis of Novel Chalcone and Pyrazoline Sulfonamide Derivatives as Potential Antibacterial Agents. Russ. J. Bioorganic Chem. 46, 371–381 (2020). https://doi.org/10.1134/S1068162020030048
22. ÇELİK, G.: Yeni pirazolin türevlerinin sentezi ve yapı karakterizasyonu. Gümüşhane Üniversitesi Fen Bilim. Enstitüsü Derg. 11, 622–628 (2021). https://doi.org/10.17714/gumusfenbil.830149
23. Farghaly, T.A., Hassaneen, H.M.E., Elzahabi, H.S.A.: Eco-friendly synthesis and 2D-QSAR study of novel pyrazolines as potential anticolon cancer agents. Med. Chem. Res. 24, 652–668 (2015)
24. Kumar, S., Bawa, S., Drabu, S., Kumar, R., Gupta, H.: Biological activities of pyrazoline derivatives-A recent development. Recent Pat. Antiinfect. Drug Discov. 4, 154–163 (2009)
25. Gailan, M.H., Hussein, M.S., Elmasry, G.F.: Samarra Journal of Pure and Applied Science Synthesis , identification , and antibacterial activity screening of some 1 H - tetrazol-5-amine derivatives. Samarra J. Pure Appl. Sci. 6, 81–95 (2024)
26. Liu, J.-J., Zhao, M., Zhang, X., Zhao, X., Zhu, H.-L.: Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents. Mini Rev. Med. Chem. 13, 1957–1966 (2013)
27. Farag, A.M., Mayhoub, A.S., Eldebss, T.M.A., Amr, A.E., Ali, K.A.K., Abdel‐Hafez, N.A., Abdulla, M.M.: Synthesis and Structure‐Activity Relationship Studies of Pyrazole‐based Heterocycles as Antitumor Agents. Arch. Pharm. (Weinheim). 343, 384–396 (2010)
28. Issa, S., Prandina, A., Bedel, N., Rongved, P., Yous, S., Le Borgne, M., Bouaziz, Z.: Carbazole scaffolds in cancer therapy: a review from 2012 to 2018. J. Enzyme Inhib. Med. Chem. 34, 1321–1346 (2019). https://doi.org/10.1080/14756366.2019.1640692
29. O’Keefe, S.J.D.: Diet, microorganisms and their metabolites, and colon cancer. Nat. Rev. Gastroenterol. Hepatol. 13, 691–706 (2016). https://doi.org/10.1038/nrgastro.2016.165
30. Moreno, L.M., Quiroga, J., Abonia, R., Lauria, A., Martorana, A., Insuasty, H., Insuasty, B.: Synthesis, biological evaluation, and: In silico studies of novel chalcone: In pyrazoline-based 1,3,5-triazines as potential anticancer agents. RSC Adv. 10, 34114–34129 (2020). https://doi.org/10.1039/d0ra06799g
31. Vichai, V., Kirtikara, K.: Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protoc. 1, 1112–1116 (2006). https://doi.org/10.1038/nprot.2006.179
32. Houghton, P., Fang, R., Techatanawat, I., Steventon, G., Hylands, P.J., Lee, C.C.: The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity. Methods. 42, 377–387 (2007). https://doi.org/10.1016/j.ymeth.2007.01.003
33. Allam, R.M., Al-Abd, A.M., Khedr, A., Sharaf, O.A., Nofal, S.M., Khalifa, A.E., Mosli, H.A., Abdel-Naim, A.B.: Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid metabolism within prostate cancer cells. Toxicol. Lett. 291, 77–85 (2018). https://doi.org/10.1016/j.toxlet.2018.04.008
34. F Mohamed, M., S Mohamed, M., M Fathi, M., A Shouman, S., Abdelshafy Abdelhamid, I.: Chalcones incorporated pyrazole ring inhibit proliferation, cell cycle progression, angiogenesis and induce apoptosis of MCF7 cell line. Anti-Cancer Agents Med. Chem. (Formerly Curr. Med. Chem. Agents). 14, 1282–1292 (2014).
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Notice
Authors retain copyright and grant the SJPAS journal right of first publication, with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in Samarra Journal of Pure and Applied Science.
The Samarra Journal of Pure and Applied Science permits and encourages authors to archive Pre-print and Post-print items submitted to the journal on personal websites or institutional repositories per the author's choice while providing bibliographic details that credit their submission, and publication in this journal. This includes the archiving of a submitted version, an accepted version, or a published version without any Risks.
