Date of Completion
Bachelor of Science in Biochemistry
Molecular Docking Simulation, Breast Neoplasms
Breast cancer is the most common type of malignancy in women and still one of the greatest healthcare dilemmas worldwide. Currently, the search for a more effective and safe treatment that is derived from natural products is still ongoing as most of the known potent drugs show many adverse effects to breast cancer patients. In this paper, the secondary metabolites from Laportea interrupta were evaluated through in silico methods of molecular docking, ADME and toxicity analyses. The molecular docking analysis performed using AutoDock Vina revealed that among the secondary metabolites in Laportea interrupta, 4-p-coumaroylquinic acid (-6.2 kcal/mol), brassidin (-6.1 kcal/mol), luteolin (-6.0 kcal/mol), and quercetin (-6.0 kcal/mol) have lowest binding energies and potentially exhibited the most stable interaction with the UBC13 enzyme. However, due to their binding energy values being relatively close to the binding energy of the reference drug molecule, Neratinib (-5.9 kcal/mol), derivatization on one of the identified top-ranked molecules was performed. The basis in determining the ligand molecule to be derivatized was the SwissADME analysis, wherein it was revealed that 4-p-coumaroylquinic acid should undergo derivatization as it exhibited the least deviation from the bioavailability radar. The cyclopentadienylsulfone derivative of 4-p-coumaroylquinic acid produced the highest binding energy value, -7.6 kcal/mol, among all the docked ligands with mostly hydrophobic bonds upon binding. Through SwissADME analysis, the relevant properties to be considered in drug development was predicted where most of the properties of the derived compound fit the pink shaded area of bioavailability radar which indicates the optimal range. The toxicity analyses have predicted that the derived compound exhibited a low possibility of inducing mutations, arrhythmias, and hepatotoxicity, as well as probable efficacy against breast cancer due to its antimetastatic and antineoplastic activity. The derived compound significantly produced better results in all analyses, hence, it is the best candidate for drug development among all the molecules. Derivatization of the other secondary metabolites, molecular dynamics, in vivo and in vitro analyses for further optimization and verification are recommended.
Margel C. Bonifacio
Echanique, A. P., Set, D. L., & Tangog, R. G. (2021, July). Molecular docking studies of selected secondary metabolites from Laportea interrupta as potential UBC13 inhibitory for human breast cancer therapy. [Bachelor's thesis, De La Salle Medical and Health Sciences Institute]. GreenPrints. https://greenprints.dlshsi.edu.ph/bch/88/