Full Presentation Script
Slide 1 — Title Slide
Good morning/afternoon everyone.
My name is Rahul Sharma, BS-MS Chemistry student from NIT Agartala.
Today I will present my research work titled:
“Curcumin derivatives as potential inhibitors for breast cancer: Molecular Docking and
Molecular Dynamics Analysis.”
This research was carried out under the supervision of Dr. Susanta Ghanta.
In this study, we computationally designed and evaluated curcumin derivatives as potential
inhibitors for breast cancer-related protein targets.
Slide 2 — Outline of Presentation
My presentation will cover the following points:
1. Brief overview of cancer and breast cancer
2. Literature review of curcumin in cancer treatment
3. Research objectives
4. Quantum chemistry calculations and methodology
5. Work performed
6. Docking results
7. Comparison with known drugs
8. SwissADME analysis
9. ProTox toxicity analysis
10. Conclusion
11. Future scope
Slide 3 — Introduction (Cancer & Breast
Cancer)
First, let us briefly understand cancer.
Cancer is a disease characterized by uncontrolled growth and spread of abnormal cells, usually
caused by genetic mutations.
Among different cancer types, breast cancer is one of the most common cancers worldwide.
According to global statistics in 2022, around 670,000 deaths occurred due to breast cancer.
Furthermore, projections suggest that by 2050 there could be about 3.2 million new cases and 1.1
million deaths every year.
Despite advances in therapy, late-stage breast cancer still remains difficult to cure, which
highlights the need for developing new therapeutic approaches.
Slide 4 — Literature Review
Curcumin is a natural bioactive compound derived from turmeric (Curcuma longa).
It has several pharmacological properties such as:
● Anti-cancer
● Anti-inflammatory
● Antioxidant activity
Curcumin works through multiple therapeutic mechanisms, including:
1. Inducing apoptosis in cancer cells
2. Inhibiting signaling pathways such as PI3K/AKT/mTOR, HER2/EGFR, and NF-κB
3. Suppressing metastasis by inhibiting MMP-9
However, natural curcumin also has some limitations:
● Poor water solubility
● Low bioavailability
Therefore, structural modification of curcumin is required to improve its therapeutic potential.
Slide 5 — Structural Optimization
In this research, we designed optimized curcumin derivatives such as:
● 3OH
● 4OH
● S1 derivatives
These derivatives were designed to improve:
● Structural stability
● Hydrogen bonding with target proteins
● Binding affinity
Our results show that Curcumin-3OH exhibited binding energy of −9.956 kcal/mol with MMP-9,
which is slightly better than the known anticancer drug Gefitinib (−9.940 kcal/mol).
Additionally, toxicity analysis suggests that curcumin derivatives belong to toxicity class 5, indicating
a relatively safer profile compared to conventional chemotherapy drugs.
Slide 6 — Need for New Therapies
Current cancer treatments face several limitations:
● Drug resistance
● High toxicity
● Lack of target specificity
Therefore, researchers are exploring natural phytochemicals because they often show:
● Lower toxicity
● Better safety profiles
● Target-specific therapeutic action
Slide 7 — Role of Phytochemicals
Plant-based compounds play an important role in cancer therapy.
They can:
● Directly target cancer cells
● Induce programmed cell death
● Inhibit tumor growth
Among these compounds, curcumin is particularly important because it regulates multiple
cancer signaling pathways.
Slide 8 — Curcumin as an Anticancer
Compound
Curcumin is naturally found in:
● Turmeric
● Curcuma longa
● Plants of the ginger family
Its anti-cancer effects include:
● Inducing apoptosis in cancer cells
● Modulating signaling pathways
● Suppressing tumor growth and metastasis
● Exhibiting anti-angiogenic properties
Due to these properties, curcumin is considered a promising candidate for cancer therapy.
Slide 9 — Research Objectives
The main objective of this study was:
To design and evaluate curcumin derivatives as potential therapeutic agents against breast
cancer.
To achieve this objective, the following steps were performed:
1. Design of curcumin derivatives
2. Molecular docking against HER2 pathway targets
3. Comparison with known anticancer drugs
4. ADME and toxicity analysis
Slide 10 — Methodology
The methodology of this study involved several computational tools.
First, GaussView software was used to design six curcumin derivatives by modifying hydroxyl
groups.
Next, protein structures were obtained from RCSB Protein Data Bank.
Then molecular docking was performed using AutoDock 4.2.6 to evaluate binding affinity between
ligands and protein targets.
After docking, SwissADME was used to analyze pharmacokinetic properties.
Finally, ProTox-III was used to predict toxicity levels of the compounds.
Slide 11–12 — Designed Curcumin
Derivatives
Using GaussView, six derivatives were designed:
● Curcumin
● Curcumin_2OH_s3
● Curcumin_2OH_s4
● Curcumin_3OH
● Curcumin_3OH_s1
● Curcumin_4OH
These derivatives were designed mainly by modifying hydroxyl groups to improve binding
interactions with target proteins.
Slide 13–18 — Molecular Docking Results
Molecular docking was carried out against several breast cancer-related targets including:
● MMP-9
● COX-2
● PI3K-α
● HER2
● Estrogen receptor
● mTOR
● VEGF-A
The docking results show binding energies mostly greater than −8 kcal/mol, indicating strong
ligand-protein interactions.
Among the derivatives, Curcumin-3OH showed the best binding energy of −9.956 kcal/mol with
MMP-9, suggesting strong inhibition potential.
Slide 19–23 — Interaction Analysis
Interaction visualization shows that the derivatives form several interactions with the target proteins,
including:
● Hydrogen bonds
● Hydrophobic interactions
● Van der Waals interactions
These interactions stabilize the ligand-protein complex and contribute to stronger binding affinity.
Slide 24–26 — SwissADME Analysis
After molecular docking, the pharmacokinetic properties of the compounds were evaluated using the
SwissADME web tool. SwissADME helps predict important ADME properties such as absorption,
distribution, metabolism, and drug-likeness of a compound.”
The most important parameters analyzed in this study include:
1. Lipinski’s Rule of Five
Lipinski’s rule is used to evaluate drug-likeness of a molecule for oral drugs.
According to this rule, a good drug candidate should have:
● Molecular weight less than 500 g/mol
● LogP less than 5
● Hydrogen bond donors ≤ 5
● Hydrogen bond acceptors ≤ 10
Our designed curcumin derivatives follow Lipinski’s rule, indicating good potential as oral drug
candidates.
2. GI Absorption
GI absorption refers to gastrointestinal absorption, which predicts how well a compound can be
absorbed through the digestive system.
The SwissADME results predict high GI absorption, suggesting that these compounds may be
efficiently absorbed when taken orally.
3. Bioavailability Score
The bioavailability score indicates the fraction of drug that reaches systemic circulation.
In our study, the compounds show a bioavailability score of around 0.55, which indicates moderate to
good oral bioavailability.
4. BOILED-Egg Model
The BOILED-Egg model predicts:
● HIA (Human Intestinal Absorption)
● BBB (Blood–Brain Barrier penetration)
The compounds located in the white region of the BOILED-Egg plot indicate good intestinal
absorption, which supports their potential as orally active drug candidates.
5. PAINS Alerts
PAINS stands for Pan-Assay Interference Structures.
These are chemical structures that can produce false positive results in biological assays.
Our compounds show no PAINS alerts, which indicates that they are chemically reliable drug
candidates.
Slide 27–28 — Toxicity Prediction
To evaluate the safety of the designed compounds, oral toxicity prediction was performed using
the ProTox-III web server. This tool predicts toxicity levels using machine learning models
based on chemical structure.”
The key toxicity parameters include:
1. LD50 Value
LD50 refers to the lethal dose required to kill 50% of the test population.
In our analysis, the predicted LD50 value is approximately 8910 mg/kg, which indicates very low
toxicity.
Higher LD50 values generally correspond to safer compounds.
2. Toxicity Class
ProTox classifies compounds into six toxicity classes:
Toxicity Class Toxicity Level
Class 1 Extremely toxic
Class 2 Highly toxic
Class 3 Toxic
Class 4 Harmful
Class 5 Low toxicity
Class 6 Non-toxic
Our compounds fall into Toxicity Class 6, which indicates very low toxicity and good safety profile
3. Prediction Accuracy
Prediction accuracy indicates the reliability of the toxicity prediction model.
In our results, the prediction accuracy is approximately 68%, which is considered acceptable for
computational toxicity prediction.
4. Structural Similarity
Average similarity represents how closely the compound structure matches known molecules in the
database used for prediction.
Our compounds show around 66% similarity, indicating that the toxicity prediction is based on
structurally related compounds.
Slide 29–33 — Comparison with Known
Drugs
The docking results of curcumin derivatives were compared with known drugs such as:
● Gefitinib
● Everolimus
● Tamoxifen
The comparison shows that curcumin derivatives demonstrate comparable or better binding
affinity in several targets.
This suggests that optimized curcumin derivatives could serve as promising alternatives to
existing drugs.
Slide 35 — Conclusion
In conclusion:
1. Curcumin derivatives showed strong binding affinity toward key breast cancer targets.
2. Interaction analysis confirmed stable ligand-protein interactions.
3. SwissADME results indicated good drug-likeness and pharmacokinetic properties.
4. Toxicity analysis suggested a favorable safety profile.
Overall, the computational results indicate that curcumin-based derivatives may act as promising
multi-target inhibitors for breast cancer therapy.
However, further experimental validation is required.
Slide 34 — Future Scope
Future work may include:
● In-vitro and in-vivo validation of the compounds
● Advanced molecular dynamics simulations
● Structure-activity relationship optimization
● Advanced ADMET studies
● Development of nano-drug delivery systems
● Target-specific screening for different breast cancer subtypes
Final Slide — Thank You
Thank you for your attention.
I would be happy to answer any questions.