5-O-acetylpinostrobin Analogs as Breast Cancer Drugs: Docking and Linear Regression QSPR for ER Alpha Inhibitors
Anita Puspa Widiyana(a), Tri Widiandani(b), Siswandono Siswodihardjo(b*)

a)Doctoral Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia
a)Department of Pharmacy, Faculty of Medicine, Universitas Islam Malang, Malang, Indonesia
b) Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia
*prof.sis[at]ff.unair.ac.id

Abstract

Breast cancer cases in 2020 have ranked first in the world and second in Indonesia, which are generally caused by 75 percent ER alpha overexpression. Long-term use of Tamoxifen as a breast cancer drug has been shown to result in drug resistance. Therefore, it is necessary to develop cancer drugs that have better activity. This study aimed to determine the prediction of anti-breast cancer activity and the QSPR relationship of 5-O-acetylpinostrobin analogs. Prediction of anti-breast cancer activity was used by the AutoDock Tools with the type of estrogen receptor alpha (PDB: 6V87). Parameters that have been selected include free energy binding and inhibition constant. Physicochemical properties (log P, HBA, MR, and TPSA) and excretion parameters (Cltot) were determined via pkCSM online. The relationship between physicochemical properties and total clearance through the QSPR equation was determined by SPSS. The results showed that 5-O-(dimethylamino)benzoylpinostrobin has the highest affinity for ER inhibitors, as seen from the value of free energy binding of -7.86 kcal/mol and Ki of 1.73 micromolar. The best QSPR equation was Log (1/Cltot)=0.130RB-0.034MR+0.366LogP+1.534 (n=14, r=0.749, R2=0.561, F=6.825, Sig.=0.004). The physicochemical parameters that are most influenced by the QSPR equation include rotatable bond, molar refractivity, and Log P. The outcome of this research is that 5-O-(dimethylamino)benzoylpinostrobin has the potential to be developed into a breast cancer drug through ER alpha inhibitors.

Keywords: 5-O-acetylpinostrobin, breast cancer, ER alpha, molecular docking, QSPR

Topic: Bioinformatics