THE SYNTHESIS OF BISOPROLOL DERIVATIVES THROUGH ACETYLATION AND FORMYLATION REACTIONS AND THE SIMULATION OF THEIR BIOACTIVITY USING IN SILICO METHOD

• Main Author: Putu Sani Oktaviani, Ni
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/64663
• Institution: Institut Teknologi Bandung

High blood pressure is a serious disease that can affect the work of the brain, heart, and kidneys. There are 1.28 billion people aged 30-79 years suffering from high blood pressure. Therefore, one of the global targets for non-communicable diseases is to reduce the prevalence of hypertension by 33% in 2010 and 2030. In the last few decades, several studies have been carried out to find new drug compounds that have activity as beta-blockers, ACE inhibitors, and calcium channel blockers to treat hypertension. Bisoprolol is a beta-blocker drug commonly used in the treatment of hypertension. It is possible to develop the drug compound bisoprolol by synthesizing bisoprolol derivative compounds by modifying the functional group contained in bisoprolol which is expected to have good activity in treating hypertension compared to bisoprolol. This study aims to synthesize bisoprolol derivatives by modifying the secondary amine functional group on bisoprolol and to determine the potential of the synthesized compound by considering its chirality as an antihypertensive drug in silico through a molecular docking simulation approach involving several receptor proteins involved in stimulating an increase in blood pressure. From the synthesis results obtained N-acetyl bisoprolol and N-formyl bisoprolol compounds from bisoprolol compounds modified on their secondary amine groups by substituting formyl groups and acetyl groups with purity of 97.88% and 96.32%, respectively, based on the results of HPLC characterization. The docking simulation results showed that the two bisoprolol derivatives had a better binding potential than bisoprolol, the chirality of the derived compounds also affected the binding strength of the derived compounds in binding to the receptor, the racemic mixture compounds had a stronger binding ability to the receptor than compounds with a single enantiomer, with the optimum value of binding energy was 10.62 kcal/mol for the compound (RS)-N-acetyl bisoprolol and 9.58kcal/mol for the compound (RS)-N-formyl bisoprolol for calcium channel receptor protein when compared with the compound (RS)-bisoprolol with a binding energy of 8.95 kcal/mol.