Nur Sofiatul Aini, Arif Nur Muhammad Ansori, Muhammad Hermawan Widyananda, Viol Dhea Kharisma, Ahmad Affan Ali Murtadlo, Mochammad Aqilah Herdiansyah, Maksim Rebezov, Pavel Burkov, Petr Gudz, Marina Derkho, Tatyana Bezhinar, Nikolai Maksimiuk, Munawir Sazali, Hery Purnobasuki, Rollando, Aswin Rafif Khairullah, Teguh Hari Sucipto
Non-small cell lung cancer (NSCLC) presents a significant global health challenge, with its prevalence and mortality rates rising steadily. In Indonesia, Syzygium cumini (L.) Skeels, known for its flavonoid richness, has a long history in traditional medicine. However, its specific mechanisms of action against cancer, particularly in inducing apoptosis in NSCLC, have not been fully elucidated. This study utilized an in silico approach to evaluate the pro-apoptotic potential of S. cumini flavonoids against NSCLC by targeting key proteins: Bcl-2, Bax, and Caspase-3. We retrieved flavonoid structures from PubChem and protein data from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB). The drug-likeness of these compounds was assessed using Swiss ADME, adhering to Lipinski's rule of five, while their anti-NSCLC probability was predicted using PASS Online. Molecular docking and screening were performed with PyRx, and the results were visualized using Discovery Studio. Our findings identified epigallocatechin 3-O-gallate and ellagic acid as the most promising anti-NSCLC candidates. Ellagic acid demonstrated the strongest binding affinity to Caspase-3, suggesting a potent pro-apoptotic effect. Epigallocatechin 3-O-gallate, on the other hand, exhibited the lowest binding energy across multiple target proteins, particularly Bcl-2 and Bax, indicating its broad pro-apoptotic potential. These results collectively suggest that flavonoids from S. cumini may hold significant promise as a source of novel anti-NSCLC agents, warranting further in vitro and in vivo investigations. © 2025 Nur Sofiatul Aini, Arif Nur Muhammad Ansori, Muhammad Hermawan Widyananda, Viol Dhea Kharisma, Ahmad Affan Ali Murtadlo, Mochammad Aqilah Herdiansyah, et al.
Department of Biology, Universitas Airlangga, East Java, Surabaya, Indonesia; Uttaranchal Institute of Pharmaceutical Science, Uttaranchal University, Uttarakhand, Dehradun, India; Postgraduate School, Universitas Airlangga, East Java, Surabaya, Indonesia; Drug and Vaccine Innovation Research Group, Virtual Research Center for Bioinformatics and Biotechnology, East Java, Surabaya, Indonesia; Medical Biotechnology Research Group, Virtual Research Center for Bioinformatics and Biotechnology, East Java, Surabaya, Indonesia; Department of Biology, Universitas Brawijaya, East Java, Malang, Indonesia; Cancer Biology Research Group, Virtual Research Center for Bioinformatics and Biotechnology, East Java, Surabaya, Indonesia; Department of Biotechnology and Food Engineering, Ural State Agrarian University, Sverdlovsk Oblast, Yekaterinburg, Russian Federation; Department of Scientific Research, Gorbatov Research Center for Food Systems, Moscow Oblast, Moscow, Russian Federation; Institute of Veterinary Medicine, South Ural State Agrarian University, Chelyabinsk Oblast, Troitsk, Russian Federation; Institute of Medical Education, Yaroslav-the-Wise Novgorod State University, Novgorod Oblast, Veliky Novgorod, Russian Federation; Faculty of Tarbiyah and Education, Universitas Islam Negeri Mataram, West Nusa Tenggara, Mataram, Indonesia; Department of Pharmacy, Faculty of Health Sciences, Universitas Ma Chung, East Java, Malang, Indonesia; Research Center for Veterinary Science, National Research and Innovation Agency of the Republic of Indonesia, West Java, Bogor, Indonesia
