Synthesis, Characterization and Cytotoxicity Activity Study of Some Chalcones Derived from 2-(1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2-ylidene)malonaldehyde

Abstract

In this work, series of new chalcones derived from indole compounds were synthesized. In the first the compound 2-(1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2-ylidene)malonaldehyde was synthesized from the reaction of 1,1,2-trimethyl-1H-benzo[e]indole with Phosphoryl chloride in in the presence of (DMF). Schiff base (C2) was prepared by reaction of 2-(1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2-ylidene) malonaldehyde with 3-amino acetophenone and then the compounds (C3-C6) were synthesized by reacting compound (C2) with a different aryl aldehyde in the presence of potassium hydroxide. The chemical composition of the compounds was confirmed and characterized by spectroscopic techniques (FT-IR, 1H-NMR and13C-NMR). Target compounds with different concentrations were investigated for their cytotoxic activity against the human breast cancer cell line MCF7. The results showed that the compounds had promising cytotoxic activity against MCF7 cell line especially compound (2) which showed the highest inhibition at the rate of 100 µg/mL among the tested compounds at varied concentrations.

Keywords

• Indole derivatives
• Chalcones
• Schiff base
• Cytotoxicity activity

Thanks

The authors wish to thank Department of Chemistry, College of Science, University of Diyala, Iraq, for supporting this work.

References

1. 1. Sravanthi, T. V., & Manju, S. L. (2016). Indoles—A promising scaffold for drug development. European Journal of Pharmaceutical Sciences, 91, 1-10.‏
2. 2. Sayed, M., Kamal El-Dean, A. M., Ahmed, M., & Hassanien, R. (2018). Synthesis of some heter°Cyclic compounds derived from indole as antimicrobial agents. Synthetic Communications, 48(4), 413-421.
3. 3. Shafakat Ali, N. A., Ahmad Dar, B., Pradhan, V., & Farooqui, M. (2013). Chemistry and biology of indoles and indazoles: a mini-review. Mini reviews in medicinal chemistry, 13(12), 1792-1800.‏
4. 4. Xavier, A., & Srividhya, N. (2014). Synthesis and study of Schiff base ligands. IOSR Journal of Applied Chemistry, 7(11), 06-15.‏
5. 5. Abu-Dief, A. M., & Mohamed, I. M. (2015). A review on application of transition metal complexes incorporating Schiff bases.‏ REPLACE THIS REFERENCE, IT DOES NOT CONTAIN THE REQUIRED INFORMATION.
6. 6. Nafia, R. A., & Faraj, F. L. (2019). Synthesis and characterization of new indole schiff bases and study effect of the compounds on lymphatic cell in metaphase in human blood. Journal of Pharmaceutical Sciences and Research, 11(4), 1319-1326.‏
7. 7. Roc ha, J. E., de Freitas, T. S., da Cunha Xavier, J., Pereira, R. L. S., Junior, F. N. P., Nogueira, C. E. S., ... & Coutinho, H. D. M. (2021). Antibacterial and antibiotic modifying activity, ADMET study and molecular d°Cking of synthetic chalcone (E)-1-(2-hydroxyphenyl)-3-(2, 4-dimethoxy-3-methylphenyl) prop-2-en-1-one in strains of Staphyl°C°Ccus aureus carrying NorA and MepA efflux pumps. Biomedicine & Pharmacotherapy, 140, 111768.‏
8. 8. Das, P., Srivastav, A. K., & Muthukannan, M. R. (2021). A study on molecular targeted approaches to cancer therapy and the role of chalcones in chemoprevention. European Journal of Molecular & Clinical Medicine, 8(3), 3254-3267.‏

9. 9. Kedar, M. S., Shirbhate, M. P., Chauhan, R., Sharma, S., & Verma, A. (2020). Design Synthesis and Evaluation of Anticancer Pyrazole Derivatives of Chalcone Scaffold. Research Journal of Pharmacy and Technology, 13(1), 342-346.
10. 10. Özdemir, A., Altıntop, M. D., Turan-Zitouni, G., Çiftçi, G. A., Ertorun, İ., Alataş, Ö., & Kaplancıklı, Z. A. (2015). Synthesis and evaluation of new indole-based chalcones as potential antiinflammatory agents. European journal of medicinal chemistry, 89, 304-309.‏
11. 11. Khezri, M., Afghan, A., Roohi, L., & Baradarani, M. M. (2016). Vilsmeier-Haack Reaction with 2, 3, 3-Trimethyl-3H-benzo [g] indole and Its Conversion into 2-(1-aryl-1H-pyrazol-4-yl)-3, 3-dimethyl-3H-benzo [g] indoles. Organic Chemistry Research, 2(2), 120-126.‏
12. 12. Rothan, H. A., Amini, E., Faraj, F. L., Golpich, M., Teoh, T. C., Gholami, K., & Yusof, R. (2017). NMDA receptor antagonism with novel indolyl, 2-(1, 1-Dimethyl-1, 3-dihydro-benzo [e] indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy. Scientific reports, 7(1), 1-10.‏
13. 13. Freshney, R. I. (2012) . Culture of animal cell. Sixth edition. Wily liss, New York. 5th edition