Synthesis and In Vitro Antimalarial Activity of Amino Chalcone Derivatives Compounds Through Inhibition of Heme Polymerization
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Abstract
This study aims to investigate the potential of chalcone derivatives as antimalarial agents. The structure of the chalcone derivatives was designed by inserting amino substituents on acetophenone and methoxy variants on benzaldehyde to produce three amino chalcone derivatives (C1, C2, and C3). The synthesis was carried out by carrying out the Claisen-Schmidt condensation reaction with NaOH 40% as catalyst, resulting in compound yields ranging from 66% - 83%. The structure of the three compounds was determined by FTIR, MS, and 1H-NMR spectroscopy techniques, which confirmed that the compounds had structures that were in line with the desired molecular structure. The antimalarial activity test was carried out by inhibiting the heme polymerization process into hemozoin (β-hematin) using hydroxychloroquine sulfate as a positive control. Absorption measurements were carried out at two different wavelengths, namely 415 nm and 630 nm. The results of the IC50 antimalarial activity of the three compounds (C1, C2, C3) were obtained respectively at 227.61; 115.18; 260.01 µg/mL and positive control of 184.98 µg/mL. From these results, it was found that compound C2 showed better antimalarial activity compared to the other two compounds and positive control.
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References
World Health Organization., Malaria. (2024). Available at: https://www.who.int/health-topics/malaria#tab=tab_1. (Accessed: 30th August 2024)
WHO., World malaria report 2023. (2023).
Shibeshi, M. A., Kifle, Z. D. & Atnafie, S. A., Antimalarial drug resistance and novel targets for antimalarial drug discovery. Infect. Drug Resist., 13: 4047–4060 (2020).
Popovici, J., Pierce-Friedrich, L., Kim, S., Bin, S., Run, V., Lek, D., Hee, K. H. D., et al., Recrudescence, Reinfection, or Relapse? A More Rigorous Framework to Assess Chloroquine Efficacy for Plasmodium vivax Malaria. J. Infect. Dis., 219(2): 315–322 (2019).
Keputusan Menteri Kesehatan RI., Keputusan Menteri Kesehatan Republik Indonesia Nomor HK.01.07/MenKes/556/2019 Tentang Pedoman Nasional Pelayanan Kedokteran Tata Laksana Malaria. MenKes/556/2019, 1(1): 2019 (2019).
Rudrapal, M., Khan, J., Aziz, A., Dukhyil, B., Mohammed, R., Ismail, I., Attah, E. I., et al., Chalcone Scaffolds , Bioprecursors of Flavonoids : Chemistry ,. 1–21 (2021).
Rammohan, A., Reddy, J. S., Sravya, G., Rao, C. N. & Zyryanov, G. V., Chalcone synthesis, properties and medicinal applications: a review. Environ. Chem. Lett., 18(2): 433–458 (2020).
Okolo, E. N., Ugwu, D. I., Ezema, B. E., Ndefo, J. C., Eze, F. U., Ezema, C. G., Ezugwu, J. A., et al., New chalcone derivatives as potential antimicrobial and antioxidant agent. Sci. Rep., 11(1): 1–13 (2021).
Shaik, A., Bhandare, R. R., Palleapati, K., Nissankararao, S., Kancharlapalli, V. & Shaik, S., Antimicrobial, antioxidant, and anticancer activities of some novel isoxazole ring containing chalcone and dihydropyrazole derivatives. Molecules, 25(5): (2020).
Tang, Y. L., Zheng, X., Qi, Y., Pu, X. J., Liu, B., Zhang, X., Li, X. S., et al., Synthesis and anti-inflammatory evaluation of new chalcone derivatives bearing bispiperazine linker as IL-1β inhibitors. Bioorg. Chem., 98(March): (2020).
Sinha, Shweta; Medhi, B. & Sehgal, R., Chalcones as an Emerging Lead Molecule for Antimalarial Therapy: A Review. J. Mod. Med. Chem., 64–77 (2013). doi:10.12970/2308-8044.2013.01.02.1
Cheng, P., Yang, L., Huang, X., Wang, X. & Gong, M., Chalcone hybrids and their antimalarial activity. Arch. Pharm. (Weinheim)., 353(4): 1–10 (2020).
Waskitha, S. S. W., Mulyana, F. E., Riza, N. F., Stansyah, Y. M., Tahir, I. & Wahyuningsih, T. D., Qsar approach and synthesis of chalcone derivatives as antimalarial compound against plasmodium falciparum 3d7 strain. Rasayan J. Chem., 14(4): 2363–2370 (2021).
Mulyana, F. E., Waskitha, S. S. W., Pranowo, D., Khairuddean, M. & Wahyumingsih, T. D., Synthesis of chalcone derivatives with methoxybenzene and pyridine moieties as potential antimalarial agents. Pharmacia, 70(4): 1305–1313 (2023).
Anagani, B., Singh, J., Bassin, J. P., Besra, G. S., Benham, C., Reddy, T. R. K., Cox, J. A. G., et al., Identification and validation of the mode of action of the chalcone anti-mycobacterial compounds. Cell Surf., 6(May): 100041 (2020).
Ünver, Y., Tuluk, M., Kahriman, N., Emirik, M., Bektaş, E. & Direkel., New Chalcone Derivatives with Schiff Base-Thiophene: Synthesis, Biological Activity, and Molecular Docking Studies. Russ. J. Gen. Chem., 89(4): 794–799 (2019).
Leite, F. F., Hanrry, B., Oliveira, M. De., Duarte, G. D., Denise, M., Ferreira, L., Scotti, M. T., et al., Anticancer Activity of Chalcones and Its Derivatives : Review and In Silico Studies. (2023).
Michalkova, R., Kello, M., Cizmarikova, M., Bardelcikova, A., Mirossay, L. & Mojzis, J., Chalcones and Gastrointestinal Cancers: Experimental Evidence. Int. J. Mol. Sci., 24(6): (2023).
Mezgebe, K., Melaku, Y. & Mulugeta, E., Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds: A Review. ACS Omega, 8(22): 19194–19211 (2023).
Suwito, H., Jumina., Mustofa., Pudjiastuti, P., Fanani, M. Z., Kimata-Ariga, Y., Katahira, R., et al., Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - Ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: Pursuing new antimalarial agents. Molecules, 19(12): 21473–21488 (2014).
Syahri, J., Hilma, R., Nurlaili., Sari, M. K., Frimayanti, N., Ali, A. H. & Latip, J., Synthesis, Antimalarial Activities of Secondary Amine-Substituted Eugenol Compounds against Plasmodium falciparum and in silico Molecular Docking Analysis. Sains Malaysiana, 52(12): 3463–3474 (2023).
Syahri, J., Yuanita, E., Nurohmah, B. A., Armunanto, R. & Purwono, B., Chalcone analogue as potent anti-malarial compounds against Plasmodium falciparum: Synthesis, biological evaluation, and docking simulation study. Asian Pac. J. Trop. Biomed., 7(8): 675–679 (2017).
Obisesan, O. R., Adekunle, A. S., Oyekunle, J. A. O., Sabu, T., Nkambule, T. T. I. & Mamba, B. B., Development of electrochemical nanosensor for the detection of malaria parasite in clinical samples. Front. Chem., 7(FEB): 1–15 (2019).
Huy, N. T., Uyen, D. T., Maeda, A., Trang, D. T. X., Oida, T., Harada, S. & Kamei, K., Simple colorimetric inhibition assay of heme crystallization for high-throughput screening of antimalarial compounds. Antimicrob. Agents Chemother., 51(1): 350–353 (2007).
Widiyati, P. N., Syamsudin, S. & Simanjuntak, P., Karakterisasi Senyawa Penghambat Polimerisasi Heme Dari Ekstrak Etanol Buah Pare (Momordica charantia L.). J. Fitofarmaka Indones., 10(2): 53–58 (2023).
Neto, B. A. D., Beck, P. S., Sorto, J. E. P. & Eberlin, M. N., In Melting Points We Trust: A Review on the Misguiding Characterization of Multicomponent Reactions Adducts and Intermediates. Molecules, 27(21): (2022).
Narwanti, I. & Afifah, H. N. A., Conventional and Microwave-Assisted Synthesis of 4’-Bromochalchone Utilizing 4-Bromoacetophenone and Benzaldehyde as Starting Material in Alkaline Condition. JKPK (Jurnal Kim. dan Pendidik. Kim., 7(3): 346 (2022).
Nur Pratiwi, D., Utami, N., Pratimasari, D., Studi, P. S., Tinggi Ilmu Kesehatan Nasional, S. & Tengah, J., Characterization and determination of total flavonoid content of extract and fraction of papaya jantan flower (Carica papaya L.) using UV-Vis spectrophotometry. J. Ilm. Farm. (Scientific J. Pharmacy), 18(2): 219–233 (2022).
Nandiyanto, A. B. D., Oktiani, R. & Ragadhita, R., How to read and interpret ftir spectroscope of organic material. Indones. J. Sci. Technol., 4(1): 97–118 (2019).
Ikhtiarudin, I., Agistia, N., Frimayanti, N., Harlianti, T. & Jasril., Sintesis 1-(4-hidroksifenil)-3-(4-metoksifenil)prop-2-en-1-on dengan bantuan gelombang mikro dan aktivitasnya sebagai antioksidan, tabir surya, dan antibakteri. J. Kim. Sains dan Apl., 23(2): 51–60 (2020).