Research Article
Synthesis, Antiproliferative Activity and In Silico Studies of Chalcones Derived From 4-(Imidazole-1-yl)Acetophenone
Abstract
In this study, the synthesis of chalcone compounds (1-11) derived from 4-(imidazol-1-yl)acetophenone and the structure determination of these compounds by various spectroscopic methods were carried out. The anticancer activities of compounds 1-11 were examined against HeLa and PC-3 cancer cells at four different concentrations (100, 50, 25, and 5 µM) using the BrdU ELISA assay. It was determined that all molecules except compounds 1 and 6 in HeLa cancer cells and compounds 2 and 8 against PC-3 cancer cells were more active against HeLa and PC-3 than the standard drug 5-fluorouracil (5-FU). The best activity against PC-3 cancer cells was compound 4 (IC50: 1.39±0.00 µM). In addition, compound 11 (IC50: 1.58±0.01 µM) was found to have the highest activity against HeLa cancer cells. Compound 4 against PC-3 cancer cell and compound 11 against HeLa cancer cell displayed cell selective activity. The ADME properties and drug similarities of the molecules 1-11 using the SwissADME software were investigated. According to these properties, compounds 1-11 were found to obey Lipinski rules.
Supporting Institution
Amasya University Scientific Research Projects Governing Unit (BAPYB)
Project Number
FMB-BAP 22-0551
Thanks
This work was supported by Amasya University Scientific Research Projects Governing Unit (BAPYB) (Grant no: FMB-BAP 22-0551, Amasya, Turkey).
References
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Year 2023,
Volume: 10 Issue: 3, 861 - 868, 30.08.2023
Abstract
Project Number
FMB-BAP 22-0551
References
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- 2. Singh P, Anand A, Kumar V. Recent developments in biological activities of chalcones: A mini review. Eur J Med Chem [Internet]. 2014 Oct 6;85:758–77. Available from: <URL>.
- 3. Nowakowska Z. A review of anti-infective and anti-inflammatory chalcones. Eur J Med Chem [Internet]. 2007 Feb 1;42(2):125–37. Available from: <URL>.
- 4. Dimmock JR, Elias DW, Beazely MA, Kandepu NM. Bioactivities of chalcones. Curr Med Chem. 1999;6(12):1125–49.
- 5. Detsi A, Majdalani M, Kontogiorgis CA, Hadjipavlou-Litina D, Kefalas P. Natural and synthetic 2′-hydroxy-chalcones and aurones: Synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity. Bioorg Med Chem [Internet]. 2009 Dec 1;17(23):8073–85. Available from: <URL>.
- 6. Gürdere MB, Özbek O, Ceylan M. Aluminum chloride–catalyzed C-alkylation of pyrrole and indole with chalcone and bis-chalcone derivatives. Synth Commun [Internet]. 2016 Feb 16;46(4):322–31. Available from: <URL>.
- 7. Gürdere MB, Aydin A, Yencilek B, Ertürk F, Özbek O, Erkan S, et al. Synthesis, Antiproliferative and Cytotoxic Activities, DNA Binding Features and Molecular Docking Study of Novel Enamine Derivatives. Chem Biodivers [Internet]. 2020 Jul 25;17(7):e2000139. Available from: <URL>.
- 8. Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol [Internet]. 2014 Jan 9;32(1):40–51. Available from: <URL>.
- 9. Dahlin JL, Inglese J, Walters MA. Mitigating risk in academic preclinical drug discovery. Nat Rev Drug Discov [Internet]. 2015 Apr 1;14(4):279–94. Available from: <URL>.
- 10. Oruç Emre EE, Karaküçük İyidoğan A, Şahin Yağlıoğlu A, Demirtaş İ, Kurşun Aktar BS. Synthesis and structure-activity relationship study: Anticancer chalcones derived from 4’-morpholinoacetophenone. Marmara Pharm J [Internet]. 2017 Oct 3;21(4):949–60. Available from: <URL>.
- 11. Kurşun Aktar BS, Oruç-Emre EE, Demirtaş I, Yaglioglu AS, Guler C, Adem S, et al. Synthesis of novel fluorinated chalcones derived from 4′-morpholinoacetophenone and their antiproliferative effects. J Mol Struct [Internet]. 2017 Dec 5;1149:632–9. Available from: <URL>.
- 12. Mathew B, Baek SC, Thomas Parambi DG, Lee JP, Mathew GE, Jayanthi S, et al. Potent and highly selective dual‐targeting monoamine oxidase‐B inhibitors: Fluorinated chalcones of morpholine versus imidazole. Arch Pharm (Weinheim) [Internet]. 2019 Apr 21;352(4):1800309. Available from: <URL>.
- 13. Rao GE, Rahaman SA, Rani AP. Synthesis, characterization and biological evolution of nitrogenous heterocyclic ring containing chalcones. Int J Pharm Sci Rev Res [Internet]. 2017;43(2):200–7. Available from: <URL>.
- 14. Sahin Yaglioglu A, Yaglioglu MS, Tosyalıoglu N, Adem S, Demirtas I. Chemical profiling, in vitro biological activities and Pearson correlation between chemical profiling and anticancer activities of four Abies species from Turkey. South African J Bot [Internet]. 2022 Dec 1;151:600–13. Available from: <URL>.
- 15. Sahin Yaglioglu A, Eser F, Yaglioglu MS, Demirtas I. The antiproliferative and antioxidant activities of the essential oils of Juniperus species from Turkey. Flavour Fragr J [Internet]. 2020 Sep 2;35(5):511–23. Available from: <URL>.
- 16. Sıcak Y, Kekeçmuhammed H, Karaküçük İyidoğan A, Taşkın Tok T, Oruç Emre EE, Öztürk M. Chalcones bearing nitrogen-containing heterocyclics as multi- targeted inhibitors: Design, synthesis, biological evaluation and molecular docking studies. J Mol Recognit [Internet]. 2023 Jul 5;36(7):e3020. Available from: <URL>.
- 17. Balcı M. Nuclear Magnetic Resonance Spectroscopy. Education Publishing House; 2020. 464 p, Ankara.
- 18. Zhang S, Luo Y, He L-Q, Liu Z-J, Jiang A-Q, Yang Y-H, et al. Synthesis, biological evaluation, and molecular docking studies of novel 1,3,4-oxadiazole derivatives possessing benzotriazole moiety as FAK inhibitors with anticancer activity. Bioorg Med Chem [Internet]. 2013 Jul 1;21(13):3723–9. Available from: <URL>.
- 19. Zhou S, Ren J, Liu M, Ren L, Liu Y, Gong P. Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents. Bioorg Chem [Internet]. 2014 Dec 1;57:30–42. Available from: <URL>.
- 20. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep [Internet]. 2017 Mar 3;7(1):42717. Available from: <URL>.
- 21. Sicak Y. Design and antiproliferative and antioxidant activities of furan-based thiosemicarbazides and 1,2,4-triazoles: their structure-activity relationship and SwissADME predictions. Med Chem Res [Internet]. 2021 Aug 15;30(8):1557–68. Available from: <URL>.
There are 21 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Biochemistry and Cell Biology (Other), Physical Chemistry (Other) |
| Journal Section | RESEARCH ARTICLES |
| Authors | |
| Project Number | FMB-BAP 22-0551 |
| Publication Date | August 30, 2023 |
| Submission Date | June 13, 2023 |
| Acceptance Date | August 5, 2023 |
| Published in Issue | Year 2023 Volume: 10 Issue: 3 |
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