CYCLIC DIARYLHEPTANOIDS FROM GARUGA (BURSERACEAE) INDONESIA AND STUDY OF ITS POTENTIAL AS ANTI TUBERCULOSIS BY IN SILICO METHOD

• Main Author: Dwi Shabrina, Fauzia
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/64731
• Institution: Institut Teknologi Bandung

Tuberculosis is a disease that can attack the lungs. This disease is caused by the bacterium Mycobacterium tuberculosis. In 2019, Indonesia was ranked second in the world with the highest tuberculosis cases. Currently, one of the commercial inhibitors used in the treatment of tuberculosis is isoniazid (INH), which works by inhibiting InhA. However, the use of isoniazid is known to cause resistance to existing drugs and can cause some side effects. Therefore, the research for InhA inhibitors is still being carried out, including by utilizing natural compounds derived from plants. One of the plants that exist in Indonesia and has been used as a traditional medicine to treat asthma and lung infections is the genus Garuga genus (family Burseraceae). Extracts from various tissues of G. pinnata and G. floribunda from Indonesia showed various bioactivities, such as antibacterial, anticancer, and antioxidant. This plant is known to produce major secondary metabolites, namely cyclic diarylheptanoid derivatives. Phytochemical studies on Garuga Indonesia have been carried out on the stem bark and bark of G. floribunda and the stem bark of G. pinnata. However, studies on the cyclic diarylheptanoids for other tissues, such as G. floribunda twigs, and studies of their antibacterial potential are limited. This study aimed to isolate the cyclic diarylheptanoid compound from the twigs of G. floribunda, which had not been previously reported, and to analyze the potential of the cyclic diarylheptanoid compound of Garuga Indonesia (stem bark of G. pinnata and twigs of G. floribunda) by the in silico method as an anti-bacterial, especially as an anti-bacterial tuberculosis (TB) that is caused by the bacterium Mycobacterium tuberculosis. The inhibition potential of various cyclic diarylheptanoids isolated from Garuga Indonesia against InhA protein was compared to an isoniazid compound using a molecular docking simulation approach. In this study, three cyclic diarylheptanoid compounds were obtained from the twigs of Garuga floribunda, which were identified as garuganin II, garuganin I, and garuganin V. These three compounds have been previously reported from the stem bark of G. floribunda, and garuganin II was also isolated from the stem bark of G. pinnata. Molecular docking simulations showed that five compounds with the best potential as InhA inhibitors were obtained, namely garuganin I, garugamblin I, GP8 (diphenyl ether type), garuganin V and alnusdiol (biphenyl type), with docking scores of 9.6, 9.6, 9.1, 8.9, 8.8 kcal/mol, respectively. Furthermore, it is suggested that the hydrogen bonding at the Tyr158 residue and the hydrophobic interactions at the binding site have a significant role in the mechanism of inhibition of diarylheptanoids against InhA.