IN SILICO STUDY OF THE POTENTIAL OF α-MANGOSTIN FROM Garcinia mangostana AND PHENYL CUMARIN AS INHIBITORS OF CANCER AND SARS-CoV-2 TARGET PROTEINS

Cancer and viral infections are two global health problems that continue to pose major challenges to medical and pharmaceutical research. Cancer is a complex disease characterized by uncontrolled cell growth and the ability to spread to other tissues, leading to high mortality rates worldwide. The COVID-19 pandemic caused by the SARS-CoV-2 virus has demonstrated how rapidly viruses can spread and impact public health, the economy, and society at large. Therefore, finding effective and safe therapies for these two diseases is a top priority (Mardianingrum et al., 2021). Developing new drugs from natural sources is a promising approach to addressing these challenges. Indonesia, as a tropical country with rich biodiversity, has great potential as a source of bioactive compounds that can be developed into innovative drugs. Tropical plants such as Garcinia mangostana, better known as mangosteen, have long been used in traditional medicine and are known to contain various bioactive compounds with broad pharmacological activities. One study examined the compound α-mangostin isolated from the rind of the mangosteen fruit (Garcinia mangostana). This compound exhibits anticancer activity through antiproliferation, apoptosis induction, aromatase inhibition, and antimetastasis mechanisms. Sub-acute toxicity testing of ethanol extract of mangosteen rind in mice for 28 days showed no significant toxic effects, indicating its safe therapeutic potential for anticancer drug development (Rusdin, 2019). One of the main compounds found in mangosteen rind is α-mangostin, a xanthone that has been extensively studied for its antioxidant, anticancer, and antiviral properties. α-Mangostin is known to inhibit cancer cell proliferation through various mechanisms, including induction of apoptosis, inhibition of cell cycle arrest, and modulation of signaling pathways involved in tumor growth and metastasis. Furthermore, α-mangostin also possesses potent antioxidant activity, neutralizing free radicals and reducing oxidative stress—factors that contribute to the development of cancer and various other chronic diseases. Sub-acute toxicity studies in animals have also shown that α-mangostin is relatively safe for use, thus increasing the potential of this compound as a drug candidate.(Yanura, 2016). The COVID-19 pandemic that has gripped the world since late 2019 has driven the urgent need for effective antiviral therapies. The SARS-CoV-2 virus has several target proteins critical for replication and infection, such as the main protease (Mpro) and the spike protein, which play a role in the virus's entry into host cells. Finding compounds that can inhibit the function of these proteins has become a major focus in antiviral drug development. Phenylcoumarin, a compound also found in several Indonesian plants, has shown potential as an inhibitor of SARS-CoV-2 target proteins based on in silico studies. A study identified the potential of bioactive compounds from Indonesian plants as antiviral agents for SARS-CoV-2 through virtual screening. The results showed that phenylcoumarin and 6-hydroxy-8-methoxy-flavanone compounds have low binding energy to the SARS-CoV-2 target protein, indicating strong affinity and stability of the interaction. This finding opens up opportunities for the development of natural compounds as effective antiviral therapies.(Özdemir et al., 2020)This compound has a low binding energy to the viral target protein, indicating strong affinity and stability of the interaction, thus potentially inhibiting viral activity effectively. The use of computational technology, particularly molecular docking and molecular dynamics simulations, allows researchers to quickly and efficiently predict interactions between bioactive compounds and protein targets. This in silico approach is particularly useful for screening potential compound candidates before proceeding to more complex and expensive laboratory testing. Thus, research that integrates Indonesia's biodiversity and modern computational technology can accelerate the process of discovering new, effective and safe drugs.(Amin et al., 2023). Based on this, this study aims to evaluate the potential of α-mangostin from Garcinia mangostana and phenylcoumarin from Indonesian plants as inhibitors of cancer and SARS-CoV-2 target proteins through an in silico approach. This research is expected to make a significant contribution to the development of natural product-based therapies that can help address health challenges caused by cancer and viral infections, as well as opening opportunities for further, more in-depth and applicable research in the future.