Feasibility Study on the Development of New Antimalarial Drugs Using Halofuginone and its Derivatives

Weilin Yan

doi:10.62051/ijphmr.v1n3.04

Authors

Weilin Yan

DOI:

https://doi.org/10.62051/ijphmr.v1n3.04

Keywords:

Halofuginone Derivatives, Antimalarial Activity, Safety Profile, Drug Discovery

Abstract

This article discusses the feasibility study entailing an innovative design in the manufacture of antimalarial drugs using Halofuginone and its derivatives as the active ingredients. Malaria is still a significant public health problem in the 21st century. Going beyond well-known approaches, novel treatment modalities should be studied. The research evaluates the ability of Halofuginone derivatives to stop the progression of Malaria, displaying great promise as a successful alternative for treating this disease. The experiment provides proof of the antimalarial efficacy of Halofuginone as an anti-Plasmodium (P. falciparum), finding about their possible mechanisms of action using structural research. Ideally, alterations are carried out to limit its toxicity, but the same task with posing their own challenges is maintaining a safety profile. The advantages of compounds prepared based on Halofuginone as candidates for clinical trials were considered, and collaboration and financial support were said to be potential facilitators. Overall, the study reinforces the efficacy of Halofuginone derivatives in Malaria and underscores the value of natural products in drug discovery.

References

Kingston, D. G., & Cassera, M. B. (2022). Antimalarial natural products (pp. 1-106). Springer International Publishing.

Balde, M. A. (2021). Phytochemical, antimicrobial and antimalarial investigations on Guinean plant species (Doctoral dissertation, University of Antwerp).

Das, S., Misra, A. J., Habeeb Rahman, A. P., Basu, A., Mishra, A., Tamhankar, A. J., & Tripathy, S. K. (2020). Designing novel photocatalysts for disinfection of multidrug-resistant waterborne bacteria. Nanotechnology for Energy and Environmental Engineering, 44, 441-476.

Tve, M. A., Payne, N. C., Johansson, C., Singh, K., Santos, S. A., Fagbemi, T.,... & Mazitschek, R. (2022). Elucidating the path to Plasmodium falciparum prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance. Nature Communications, 13(1), 4976.

Gill, J., & Sharma, A. (2022). Prospects of halofuginone as an antiprotozoal drug scaffold. Drug Discovery Today, 27(9), 2586-2592.

Nyamaji, D. W., & Tasta, Bishop, Ö. (2020). Identification of selective novel hits against Plasmodium falciparum prolyl-tRNA synthetase active site and a predicted allosteric site using in silico approaches. International Journal of Molecular Sciences, 21(11), 3803.

Yogavel, M., Boundou, A., Mishra, S., Malhotra, N., Chhibber-Goel, J., Bellini, V.,... & Sharma, A. (2023). Targeting prolyl-tRNA synthetase via a series of ATP-competitive tools to accelerate drug discovery against toxoplasmosis. Plos Pathogens, 19(2), e011124.

Zhang, S., Cai, J., Xie, Y., Zhang, X., Yang, X., Lin, S.,... & Zhang, J. (2022). Anti-phytophthora activity of halofuginone and the corresponding mode of action. Journal of Agricultural and Food Chemistry, 70(39), 12364-12371.

Deng, Y., Wu, T., Zhai, S. Q., & Li, C. H. (2019). Recent progress on anti-Toxoplasma drugs discovery: Design, synthesis and screening. European Journal of Medicinal Chemistry, 183, 11171.

Zhang, Z., Zhou, L., Xie, N., Nie, C. E., Zhang, T., Cui, Y., & Huang, C. (2020). Overcoming cancer therapeutic bottleneck by drug repurposing. Signal Transduction and Targeted Therapy, 5(1), 113.

Rashidzadeh, H., Tabakbaeirezai, S. J., Adyani, S. M., Abazari, M. R., Rahamooz-Haghighi, S., & Abdollahi, H., & Ramazani, A. (2021). Recent advances in targeting malaria with nanotechnology-based drug carriers. Pharmaceutical Development and Technology, 26(8), 807-823.

Wang, M., Xu, X. R., Bai, Q. X., Wu, L. H., Yang, X. P., Yang, D. Q., & Kuang, H. X. (2024). Dichroa febrifuga Lou.: A review of its botany, traditional use, phytochemical activities, and toxicology. Journal of Ethnopharmacology, 189, 110893.

Ismail, F. M. (2019). Nature’s armamentarium against malaria: antimicrobials and their semisynthetic derivatives. Molecules and Natural Product Derivatives, 333, 333-373.

Kumar, A., Devan, A. R., Nair, B., & Nath, L. R. (2021). Anti-VEGF mediated immunomodulatory role of phytochemicals: scientific exposition for plausible HCC treatment. Current Drug Targets, 22(11), 1288-1316.

Surve, D. H., Bhide, A., Jindal, A. B., & Devarajan, P. V. (2023). Nanomedicines for the Treatment of Veterinary Parasitic Infections. In Nanomedicines for the Prevention and Treatment of Infectious Diseases (pp. 149-196). Cham: Springer International Publishing.

Pang, L. (2020). Structural Characterization of Aminoacyl-tRNA Synthetase Inhibitors as Antibiotics and Tools for Enzyme Mechanistic Studies. Mechanistic Insights into Bioactive Peptides, 129, 129-150.

Hatzakis, E. (2019). Nuclear magnetic resonance (NMR) spectroscopy in food science: A comprehensive review. Comprehensive Reviews in Food Science and Food Safety, 18(1), 189-220.

Cao, R., Liu, X., Liu, Y., Zhai, X., Cao, T., Wang, A., & Qiu, J. (2021). Applications of nuclear magnetic resonance spectroscopy to the evaluation of complex food constituents. Food Chemistry, 342, 128528.

Koshanin, R., Jafari, S. M., & van de Ven, T. G. (2020). Going deep inside bioactive-loaded nanocarriers through Nuclear Magnetic Resonance (NMR) spectroscopy. Trends in Food Science & Technology, 101, 198-212.

Kumar, A., Ghosh, D. K., Ali, J., & Ranjan, A. (2019). Characterization of lipid binding properties of plasmodium falciparum acyl-coenzyme A binding proteins and their competitive inhibition by mefloquine. ACS Chemical Biology, 14(5), 901-915.

Cullia, G., Bruno, S., Parapini, S., Marigotta, M., Tamborini, L., Pinto, A.,... & Conti, P. (2019). Covalent inhibitors of Plasmodium falciparum glyceraldehyde-3-phosphate dehydrogenase with antimalarial activity in vitro. ACS Medicinal Chemistry Letters, 10(4), 590-595.

Peng, X., Wang, N., Zhu, A., Xu, H., Li, J., Zhou, Y.,... & Deng, D. (2021). Structural characterization of the Plasmodium falciparum lactate transporter PfENT alone and in complex with antimalarial compound MMV007839 reveals its inhibition mechanism. Plos Biology, 19(9), e301386.

Kucharski, D. J., Jeszka, M. K., & Baranowski, P. J. (2022). A review of modifications of quinoline antimalarials: methoquine and hydroxychloroquine. Molecules, 27(3), 1003.

Siqueira-Neto, J. L., Wick, J. C., Choi, K., Burrows, J. N., Fidock, D. A., & Winzeler, E. A. (2023). Antimalarial drug discovery: Progress and approaches. Nature Reviews Drug Discovery, 21(10), 807-826.

Jagoe, H. (2021). New approaches to antimalarial target deconvolution and measuring effects of Plasmodium falciparum mutations implicated in drug resistance (Doctoral dissertation).

Jain, P. P., Zhao, T., Xiong, M., Song, S., Lai, N., Zheng, Q., & Yuan, J. X. J. (2021). Halofuginone, a promising drug for treatment of pulmonary hypertension. British Journal of Pharmacology, 178(17), 3373-3394.

Goloboff, N., Ishak, S. A., Shahar, A. I. R., Roslan, N. A., & Ghazali, R. (2019). Good laboratory practice (GLP) for greater compliance in an increasingly regulated market. Palm Oil Developments, 71, 33-40.

Lx, T., Huang, J., Wu, M., Wang, H., Zeng, Q., & Wang, X. (2022). Halofuginone enhances the anti-tumor effect of ALA-PDT by suppressing NRF2 signaling in CSCC. Photodiagnosis and Photodynamic Therapy, 37, 105272.

Rathmes, G., Rumisha, S. F., Lucas, T. C., Twohig, K. A., Python, A., Nguyen, M.,... & Weiss, D. J. (2020). Global estimation of antimalarial drug effectiveness for the treatment of uncomplicated Plasmodium falciparum malaria 1991–2019. Malaria Journal, 19, 1-15.

Obradovic, M., Gunic, R., & Kaurin-Sarac, B. R. APPLICATION OF THE PRINCIPLES OF GOOD LABORATORY PRACTICE IN THE LABORATORYORIES OF THE COLLEGE OF HEALTH SCIENCES PERIOD. In Scientific/Technical Issues 2023 (p. 413).

Davis, T. C., Arnold, C. L., Mills, G., & Miele, L. (2019). A qualitative study exploring barriers and facilitators of enrolling underrepresented populations in clinical trials and biobanking. Frontiers in Cell and Developmental Biology, 7, 74.

Bodiocat, D. H., Routen, A. C., Willis, A., Ekezie, W., Gillies, C., Lawson, C.,... & Khunti, K. (2021). Promoting inclusion in clinical trials—a rapid review of the literature and recommendations for action. Trials, 22, 1-11.

Pang, L., Weeks, S. D., & Van Aerschot, A. (2021). Aminoacyl-tRNA synthetases as valuable targets for antimicrobial drug discovery. International Journal of Molecular Sciences, 22(4), 1750.