Tangerang International Conference 2021

Summary

This research presents an in silico study aimed at developing a new anti-cancer compound by modifying chemical structures to target the enzyme sirtuin 1. The study uses molecular docking simulations to predict compound interactions with cancer cell receptors. The results demonstrate that the test compound is more stable and exhibits superior pharmacological properties compared to a comparison compound. It also adheres to Lipinski's Rule of Five, suggesting potential for oral drug use. The findings highlight the compound's promise as a lead candidate for further development in cancer treatment.

Takeaways

• 😀 Cancer is a leading cause of mortality, prompting the development of anti-cancer therapies targeting key proteins like CIRCUIT1.
• 😀 CIRCUIT1, a member of the Sirtuin 2 family, is involved in regulating critical biological processes, making it a target for cancer therapy.
• 😀 Tiaura derivatives have potential anti-cancer properties, including activity against the nervous system, antimicrobials, and anti-inflammatory effects.
• 😀 In-silico techniques were employed to predict the chemical properties, toxicity, and receptor interactions of the compound to accelerate drug development.
• 😀 The study utilized various software tools such as Chambra Ultra, Molecular View, and Discovery Studio to design and test the compound.
• 😀 The docking simulation revealed that the designed compound had a better binding affinity (−8.36 kcal/mol) compared to the comparison compound (−6.29 kcal/mol).
• 😀 The test compound demonstrated more stable interactions with cancer receptors, with 10 hydrophobic and 2 heteroatom interactions.
• 😀 The compound passed the Lipinski Rule of 5, suggesting it is suitable for oral administration with minimal toxicity.
• 😀 The free energy binding results and the RMSD value (0.375) indicated that the docking results were valid and stable.
• 😀 The research concluded that the test compound has potential as an oral cancer drug candidate, though some restrictions based on its similarity to other compounds remain.

Q & A

What is the main focus of the research presented in the transcript?

The main focus of the research is the in silico study of a cancer treatment compound, specifically its interaction with cancer cell receptors. The research aims to design and develop a more effective anti-cancer drug through molecular modification.

What role does 'circuin one' play in cancer therapy according to the presentation?

'Circuin one' is a member of the histone acetyltransferase family and plays a significant role in cancer therapy. It is a target for drug development because it influences cancer cell growth, making it a key focus in the design of anti-cancer treatments.

Why are in silico methods used in drug discovery in this research?

In silico methods are used to predict the chemical properties, toxicity, and drug-receptor interactions of compounds. This computational approach accelerates the drug discovery process by providing insights into the potential effectiveness and safety of compounds before conducting physical experiments.

What is molecular docking and how was it used in this research?

Molecular docking is a computational technique used to predict how a compound binds to a target receptor. In this research, molecular docking was employed to assess the binding affinity of the test compound with cancer cell receptors and compare it to a reference compound.

What were the key findings from the molecular docking results?

The key finding from the molecular docking results was that the test compound showed a stronger binding affinity to the cancer cell receptor than the comparison compound. The test compound had a binding free energy of -8.36 kcal/mol, compared to -6.29 kcal/mol for the comparison compound.

How did the test compound perform in terms of receptor interaction compared to the comparison compound?

The test compound formed more stable interactions with the receptor, including hydrogen bonds and hydrophobic interactions. It exhibited greater stability due to a higher number of interactions compared to the comparison compound.

What is Lipinski's Rule of Five, and why is it important in this research?

Lipinski's Rule of Five is a set of criteria used to predict whether a compound has properties that would make it a good oral drug. The rule assesses molecular weight, lipophilicity, hydrogen bonding, and other factors. In this research, the test compound satisfied these criteria, indicating its potential as an oral drug.

What does the negative binding free energy value indicate in the context of drug binding?

A negative binding free energy value indicates that the compound has a strong binding affinity for its target receptor. The more negative the value, the stronger the interaction, suggesting that the compound is more likely to be an effective drug candidate.

What were the tools and software used in this study for molecular modeling?

The tools and software used in this study include ChemBioDraw Ultra 8.0, Molecular View, Discovery Studio, and online servers for predicting chemical properties and toxicity, such as the Pikachu GSM web server.

What are the potential next steps for this research after the initial in silico findings?

The next steps include conducting further in vitro experiments to validate the results obtained from the in silico study, as well as exploring the pharmacokinetic properties and toxicity of the test compound in greater detail.