Discovery and Design of Xanthone Derivatives as InhA Inhibitors for Antituberculosis Agents Using Virtual Screening and Molecular Dynamics Simulations
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Abstract
This research aimed to identify novel anti-tuberculosis compounds from xanthone derivatives effectively inhibiting InhA activity. A total of 19,856 xanthone structures were retrieved from the PubChem database and subjected to virtual screening. Three promising xanthone compounds demonstrating key interactions and strong binding affinity with the InhA enzyme were selected. These compounds were further analyzed to investigate their binding modes and key interactions within the InhA active site using molecular dynamics simulations. The results revealed that the hydroxyl groups attached to the xanthone core played a crucial role in forming hydrogen bond interactions with the amino acid Tyr158 and the NADH cofactor, thereby enhancing their inhibitory efficacy against InhA. Additionally, compound 1 exhibited hydrophobic interactions with non-polar amino acid residues in the InhA binding pocket, including Phe149, Met155, Pro156, Ala157, Pro193, Met199, and Leu218. Based on these findings, a promising InhA inhibitor was rationally designed using compound 1 as a template, demonstrating improved efficacy. The results of this study provide valuable molecular-level structural insights, contributing to the development of promising new anti-tuberculosis agents in the future.
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บทความที่ได้รับการตีพิมพ์เป็นลิขสิทธิ์ของ วารสารวิทยาศาสตร์และเทคโนโลยี มหาวิทยาลัยอุบลราชธานี
ข้อความที่ปรากฏในบทความแต่ละเรื่องในวารสารวิชาการเล่มนี้เป็นความคิดเห็นส่วนตัวของผู้เขียนแต่ละท่านไม่เกี่ยวข้องกับมหาวิทยาลัยอุบลราชธานี และคณาจารย์ท่านอื่นๆในมหาวิทยาลัยฯ แต่อย่างใด ความรับผิดชอบองค์ประกอบทั้งหมดของบทความแต่ละเรื่องเป็นของผู้เขียนแต่ละท่าน หากมีความผิดพลาดใดๆ ผู้เขียนแต่ละท่านจะรับผิดชอบบทความของตนเองแต่ผู้เดียว
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