IN SILICO ANALYSIS OF SECONDARY METABOLITES FROM CRYPTOCARYA PULCHRINERVIA LEAVES (LAURACEAE)
Cancer disease can occur when the cycle and cell division are not controlled. One of the cancer diseases that can cause the highest death is breast cancer. There have been many researches on anticancer drugs to inhibit proteins involved in the cell cycle. Some commercial drugs to treat breast cancer...
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| Format: | Final Project |
| Language: | Indonesia |
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| Online Access: | https://digilib.itb.ac.id/gdl/view/55099 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Cancer disease can occur when the cycle and cell division are not controlled. One of the cancer diseases that can cause the highest death is breast cancer. There have been many researches on anticancer drugs to inhibit proteins involved in the cell cycle. Some commercial drugs to treat breast cancer include palbociclib, ribociclib, and amebaciclib. All three drugs work by inhibiting the CDK4/6 protein in the cell cycle. However, the three drugs still have various side effects. Therefore, the search for anticancer drugs with minimal side effects is still underway. One source of anticancer drugs is natural compounds, especially those were obtained from plants. One of the plants in Indonesia that has been reported to produce compounds having potential anticancer is Cryptocarya genus (Lauraceae). Research on one of the Cryptocarya species growing in Indonesia, namely the leaves tissues of C. pulchrinervia which reported the presence of four pyrone compounds, in which three of them, namely pulchrinervialacton A, (S)-rugulactone and cryptobrachytone C, had significant activity to inhibit murine leukemia P-
388 cells and another pyrone, i.e. pulchrinervialactone B, is inactive. The results of this study prompted an in silico analysis using molecular docking and molecular dynamics methods to determine and compare the mechanism of interaction between palbociclib (a commercial drug) and the four pyrone derivatives toward the CDK6 protein in cell cycle. This research has not been previously reported. The result of docking simulations and dynamics simulation have shown that pulchrinervialctone B and (S)-rugulactone had potential as CDK6 inhibitor candidates. The inhibition that occured by the two compounds was due to hydrophobic interactions with the residues in allosteric site of CDK6 without involving the formation of hydrogen bonds. The results of this study provided information about the mechanism against CDK6 at the atomic level.
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