ROTENOID DERIVATIVE FROM AMORPHA FRUTICOSA, ACTIVITY AND DOCKING STUDY AS TYROSINE KINASE RECEPTORS
Cancer is one of the major worldwide health problems. Until 2020, 10 million people has been died by cancer. Chemotherapy is one of the cancer treatment methods, but various types of drugs used in chemotherapy have dangerous side effects since their toxic effect on normal cells. Tyrosine kinase inhi...
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| Format: | Theses |
| Language: | Indonesia |
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| Online Access: | https://digilib.itb.ac.id/gdl/view/68057 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Cancer is one of the major worldwide health problems. Until 2020, 10 million people has been died by cancer. Chemotherapy is one of the cancer treatment methods, but various types of drugs used in chemotherapy have dangerous side effects since their toxic effect on normal cells. Tyrosine kinase inhibitors are chosen as drugs in cancer therapy because they are considered less toxic to normal cells. This is because tyrosine kinase inhibitors selectively inhibits phosphorylation on the receptor's active site, thus it inhibits cell proliferation and growth. Natural compounds play an essential role in the discovery and development of new drugs. Natural compounds are considered to have broad sources, better chemical diversity, and more biological relationships so natural compounds are used as better tyrosine kinase inhibitors sources. The seeds of Amorpha fruticosa contain rotenoid derivative, that contain heterocyclic rings and lots of oxygen atom, which can be active as tyrosine kinase inhibitors. Biological response is the result of the interaction of drug molecules with receptor molecules in the form of chemical interactions. Inhibitor molecular interactions with amino acid residues on receptors, can be predicted by docking studies. In this study, 4 rotenoid derived compounds were isolated, namely tephrosine (1), 11-hydroxytephrosine (2), amorphispironone (3), dalpanol (4), and 6'-O-?-D-glucopyranosyl-dalpanol (5) which was 1 rotenoid glycoside and indentified their structures by 1D and 2D NMR. The results of the tyrosine kinase inhibitor activity showed that compound 5 acted as a tyrosine kinase EGFR, HER2, and IGF1R with inhibition values of 54, 16, and 24%, respectively. The docking study showed intermolecular interactions of compound 5 with EGFR HER2 and IGF1R. The glucopyranosyl group plays a role in hydrogen binding, while the basic structure of compound 5 plays a role in hydrophobic interactions. |
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