Chemical Structure Optimization of Lupeol As ER-α and HER2 Inhibitor

Asian J Pharm Clin Res, Vol 11, Issue 6, 2018, 298-303

6 Pages Posted: 4 Aug 2018

See all articles by Mohammad Rizki Fadhil Pratama

Mohammad Rizki Fadhil Pratama

Universitas Muhammadiyah Palangkaraya


Sebelas Maret University

Date Written: June 2018


Objectives: Lupeol, a triterpenoid isolated from Kasturi (Mangifera casturi) fruit has been known for having several pharmacological activities, including anticancer properties. Lupeol showed antiproliferative activity toward many cancer cells line including breast cancer. Lupeol showed promising potency as both ER-α and HER2 inhibitors, although still lower than known ER-α and HER2 Inhibitors. Chemical structure optimization of lupeol was predicted could increase the affinity of lupeol derivatives against ER-α and HER2. This study aims to determine lupeol derivative with the highest affinity against ER-α and HER2. Methods: All ligands were sketched and optimized using Gaussian 03W with Hartree–Fock method basis set 3-21G. Molecular docking was performed using Autodock 4.2.6 on several modified chemical structure of lupeol against active site of ER-α and HER2. The main parameter used was the free energy of binding and inhibition constants as affinity marker. Results: The docking results show that lupeol derivative with an amine group (Lupeol-2) and ethyl group (Lupeol-4) at position C3 provide the highest affinity with the free energy of binding and dissociation constant −12.24 kcal/mol and 1.07 nM for ER-α also −9.63 kcal/mol and 86.94 nM for HER2, respectively. Interestingly, although lupeol derivatives showed higher affinity toward ER-α, their amino acid residues were closer to the interaction on HER2. Conclusion: These results predict that lupeol have greater potential to be developed as a HER2 inhibitor. Further, derivate lupeol-4 should be potential to be developed as HER2-positive breast cancer therapy.

Keywords: Breast Cancer, Docking, ER-α, HER2, Lupeol

Suggested Citation

Pratama, Mohammad Rizki Fadhil and Sutomo, Chemical Structure Optimization of Lupeol As ER-α and HER2 Inhibitor (June 2018). Asian J Pharm Clin Res, Vol 11, Issue 6, 2018, 298-303. Available at SSRN:

Mohammad Rizki Fadhil Pratama (Contact Author)

Universitas Muhammadiyah Palangkaraya ( email )

RTA Milono Street Km. 1.5
Palangka Raya, Central Kalimantan 73111



Sebelas Maret University ( email )

Jl. Ir. Sutami 36A
Surakarta, Jawa Tengah 57126

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