ABSTRACT:
Breast cancer indicated uncontrollably proliferation and spread of cells that related to HER2 overexpression. In 2020, Indonesia showed the highest prevalence of breast cancer with 65.858 cases. Several therapeutic methods had been carried out, including chemotherapy, and radiation therapy. However, it induced various side effect during the treatment. Herbs are considered as an alternative therapy for treatment. The calamansi orange peel is considered as a waste, yet it known for containing various therapeutic properties. The therapeutic efficacy of calamansi orange peel in the treatment of breast cancer requires more investigation. Thus, the purpose of this study was to determine the potency of compounds from calamansi orange’s peel against breast cancer. Five compounds of calamansi orange peel were collected as a sample from PubChem database. Those compounds were addressed for several analysis, such as analysis of biological activity by using PASS Online, toxicity analysis by using ProTox 3.0, and drug-likeness analysis by using SWISS ADME. Furthermore, HER2 protein was selected as a protein target. The interaction between sample compounds and protein target was simulated through molecular docking analysis by using PyRx software and continued with amino acid residue analysis. Moreover, further analysis toward HER2 protein was conducted through protein-protein network analysis using STRING database. Result showed that all sample compounds had biological activity related to anticancer activity, such as antineoplastic, apoptosis agonist, and anti-inflammatory with Pa score 0.5 – 0.7. Moreover, the drug-likeness analysis according to Lipinski’s rule of five depicted that all sample compounds fulfil the required parameters. Those compounds also demonstrated low toxicity level with average toxicity class 4 and 5. Interaction of compounds toward protein target demonstrated all sample compound had comparable binding affinity score as compared to native ligand and reference ligand. In brief, 3-Isopropenyl-5,5-Dimethyl-Cyclopentene had binding affinity -6,5 kcal/mol. The native ligand and sample compound both shared amino acid residues in Ala751, Met774, Ser783, Leu785, and Thr862. Additionally, HER2 protein depicted a link to the immune system, and cell proliferation pathway. Thus, compounds derived from calamansi orange peel considered had potential therapeutic effect for breast cancer treatment.