HUBUNGAN KUANTITATIF STRUKTUR-AKTIVITAS TURUNAN TETRAHIDROPYRAZOLO-QUINAZOLIN SEBAGAI KANDIDAT SENYAWA ANTIKANKER PROSTAT
Prostate cancer is an adenocarcinoma which occurs when cells in the prostate gland divide continuously and also one of the biggest causes of death in the world with 1.28 million deaths in 2018. In this research, correlation of the activity of tetrahydropyrazolo-quinazoline derivative compounds ag...
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| Format: | Final Project |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/47057 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Prostate cancer is an adenocarcinoma which occurs when cells in the prostate gland divide
continuously and also one of the biggest causes of death in the world with 1.28 million deaths in 2018.
In this research, correlation of the activity of tetrahydropyrazolo-quinazoline derivative compounds
against c-Met was done by determining the IC50 prediction value. The purpose of this study was to
conduct a deeper study of the physicochemical properties of tetrahydropyrazolo-quinazoline
derivative compound and biological activity through determining the best quantitative structureactivity relationship study (QSAR). QSAR is a method used to eliminate the element of luck in drug
design by linking chemical structures and biological activities quantitatively, and includes statistical
methods that are associated with structural elements and physicochemical parameters. The test was
carried out using 45 compounds data as a training set compound which had an IC50 value from in vitro
experimental results. The best QSAR equation obtained was Log IC50 (µM) = 6,9108485819
(±1,4108774136) + 0,0711972245 (±0,0354346249) x LogP(o/w) + 0,0073707405 (±0,0065379292) x
Vol + 0,0001810478 (±0,0000150557) x AM1_E - 0,0000123926 (±0,0000021372) x AM1_Eele. As many
as 92 models of new derivative compounds were designed from the lead compound based on the Craig
curve and QSAR equation. From 92 models designed, there were 10 compounds which had a lower IC50
value than the lead compound which are A8, YR11, YR13, YR16, YR21, YR26, YR31, YR36, YR61 and
YR66. The compound was then analyzed for the results of docking with the c-Met receptor using
BIOVIA Discovery Studio 2017 and the best compound candidate was obtained which was YR16 based
on free energy, the number of hydrogen bonds and amino acid residues.
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