# A Computational (DFT) Study on the Anti-Malarial Drug: Lumefantrine
## 1 Introduction  
Malaria is a parasitic disease in humans that causes thousands of deaths every year [1]. According to World Malaria Report 2020 by WHO, 409,000 people die because of this disease every year. As a promising development from the same report, the malaria deaths reduced from 736,000 to 409,000 between the years 2000 and 2019. The report also underlines that globally an estimated 1.5 billion malaria cases and 7.6 million malaria deaths have been prevented in the same period [2]. Lumefantrine is an amino alcohol developed by Chinese scientists at around the same time as medioquine. It has been the mainstay of the most widely used combination therapy with artemether. So far a significant resistance has not been seen because Lu-mefantrine has never been used as monotherapy [3]. Lumefantrine has been used with artemether since 1994. Bombarded by two different drugs with different destructive mechanisms, the parasite cannot develop a resistance against both [4]. Artemether, a potent anti-malarial drug derived from the sweet wormwood plant (Artemisia annuua), has become a pivotal tool in combating malaria, particularly infections caused by drug-resistant Plasmodium falciparum parasites. With over 200 million malaria cases reported annually, the disease continues to pose a significant global health threat, particularly in sub-Saharan Africa. As a member of the artemisinin class of drugs, artemether's rapid action and ability to target both the blood-stage and drug-resistant forms of the malaria parasite make it highly effective. Its combination with other anti-malarial drugs in artemisinin-based combination therapies (ACTs) has revolutionized malaria treatment, reducing mortality and morbidity. The emergence of artemisinin resistance in certain regions demands continuous monitoring and research to preserve its efficacy and ensure effective malaria control strategies worldwide. This article aims to provide a comprehensive review of artemether's pharmacology, efficacy, safety and its role in malaria control efforts, shedding light on the current state of this critical anti-malarial agent [5, 6]. 4-Aminoquinoline is a quinoline derivative with an amino group at the 4-position of the quinoline ring. It is a key building block in medicinal chemistry and has beenextensively studied for its diverse pharmacological properties. Notably, it has been vital in anti-malarial research, with derivatives like chloroquine used to treat malaria by disrupting the heme detoxification process in the malaria parasite. Beyond anti-malarial effects, 4-aminoquinoline shows promise as an antimicrobial agent against various pathogens and has been explored for potential use in anti-cancer and anti-inflammatory treatments. Its versatility makes it a valuable template for designing novel pharmaceutical agents, making it a subject of great interest in contemporary drug development [7; 8; 9]. The physicochemical properties of the three most well-known anti-malarial compounds are briefly presented in Table 1[10; 11; 12; 13; 14]. This study has been inspired by a former study by Friedrich Research group. In their study, which has been published in an elite scientific journal, they investigated the structural and spectral properties of Lumefantrine [1]. Computational chemistry has become an invaluable tool for predicting the structural and spectral properties of small molecules, transforming various scientific fields. Its applications in chemistry, biochemistry, drug discovery and materials science have been particularly noteworthy. While experimental techniques remain essential, computational methods offer cost-effective and efficient means to gain critical insights into molecular behavior [7]. Through accurate predictions of molecular structures and spectroscopic properties, computational chemistry plays a pivotal role in understanding the conformation and interactions of small molecules. High-throughput screening capabilities aid in identifying potential candidates for drug development and materials design.