Malaria is still a health problem in the world. Five species can infect humans, namely Plasmodium falciparum, Plasmodium vivax, Plasmodium malaria, Plasmodium ovale, and Plasmodium knowlesi.Four species are considered true parasites of humans, while P. knowlesi is still considered a zoonotic malaria. Among these species, P. falciparum and P. vivax are the most prevalent worldwide, in which the most common complications of severe malaria occur in P. falciparum infection. 1 The most frequent clinical manifestation of malaria is fever or recent history of fever. However, because many diseases also have fever as primary clinical manifestation even in the endemic area, accurate laboratory parameter is crucial. False-positive will lead to improper use of antimalarial therapy, and obviously, underdiagnosed cases cause an increase in morbidity, mortality, and antimalaria resistance. 2 The most frequently used method for early detection of malaria infection and remains the gold standard for laboratory confirmation of malaria is microscopic because it is easy to use and cheap. However, there are still many weaknesses in its application. 3

Malaria is one of the life-threatening diseases in the world. The spread of resistance to antimalarial drugs is a major challenge, and resistance to artemisinin has been reported in the Southeast Asian region. In the previous study, the active compound of Streptomyces hygroscopicus subsp. Hygroscopicus (S. hygroscopicus), eponemycin, has been shown to have antimalarial effects. To further analyze the effects of other active compounds on the Plasmodium parasite, identifying and analyzing the effectiveness of compounds contained in S. hygroscopicus through instrumentation of liquid chromatography/mass spectrometry (LC/MS) and in silico studies were very useful. This study aimed at identifying other derivative compounds from S. hygroscopicus and screening the antimalarial activity of the compound by assessing the binding affinity, pharmacokinetic profile, and bond interaction. The derivative compounds were identified using LC/MS. Protein targets for derivative compounds were found through literature studies, and the results of identification of compounds and protein targets were reconstructed into three-dimensional models. Prediction of pharmacokinetic profiles was carried out using Swiss ADME. Screening of protein targets for the derivative compound was carried out using the reverse molecular docking method. Analyzing bond interaction was done by LigPlot. One compound from S. hygroscopicus, i.e., 6,7-dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione, was successfully identified using LC/MS. This compound was an isoquinoline derivative compound. Through literature studies with inclusion criteria, thirteen protein targets were obtained for reverse molecular docking. This isoquinoline derivative had the potential to bind to each protein target. The pharmacokinetic profile showed that this compound had the drug-likeness criteria. Conclusion. 6,7-Dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione has antimalarial activity as shown by reverse molecular docking studies and pharmacokinetic profiles. The best inhibitory ability of compounds based on bond affinity is with adenylosuccinate synthetase.

<p>Streptomyces hygroscopicus (S.hygroscopicus) is a Gram-positive soil bacterium that can produce secondary metabolites from fermentation that have a therapeutic effect. The fermented S. hygrocospicus metabolites that are still in the form of crude extracts are difficult to develop as drug preparations because the active compounds are not yet known, so it will be challenging to determine the dosage of drugs that have a therapeutic effect. Therefore, it is necessary to carry out exploratory research to narrow down the secondary metabolite profile from the fermentation of S. hygroscopicus, using extraction and fractionation methods, which are then identified by Thin-Layer Chromatography (TLC) using a combination of solvents. This study used the extraction method with a separating funnel. The fractionation was carried out using the BUCHI (Sepacore®) Flash Chromatography and Reveleris® PREP Purification System column chromatography gradually using ethyl acetate and n-hexana.  47 and 60 of the fractionation results were taken as samples, that further were profiled using TLC and given the appearance of 10% KOH stains and p-Anisaldehyde - sulfuric acid, so that various classes of compounds with different Rf values were obtained, namely Monoterpenes, Triterpenes, Steroids, Saponins, Coumarin, Scopoletin, and Alkaloids.</p>

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