Design, Synthesis, And Quantitative Structure-Activity Relationship of 5-O-Acylpinostrobin Derivatives As Anti-Breast Cancer Through In Silico and In Vitro

Breast cancer is a major health problem in the world. The goal of this study was to find a more active and safe derivative of 5-O- acylpinostrobin. A number of 20 5-O-acylpinostrobin derivatives were analyzed for activity, toxicity, and pharmacokinetics through in silico analysis. In silico, activity was analyzed by AutoDock (PDB: 3ERT), toxicity by ProTox 3.0, and pharmacokinetics by pkCSM. The selection of 5-O-acylpinostrobin derivatives is based on the prediction of higher activity and pharmacokinetics, lower toxicity, and availability of materials on the market. The synthesis methods were microwave irradiation, cytotoxic by MTT, and QSPR/QSAR by SPSS. The results of the in silico study selected five compounds: AP-2, AP-3, AP-4, AP-6, and AP-7. AP-3, AP-4, and AP-7 had higher cytotoxic activity on T47D cells than pinostrobin, AP-6 and AP-2 were lower than pinostrobin, and all (5) derivatives were lower than 4-OHT. AP-7 was more toxic than pinostrobin and less toxic than 4-OHT in Vero cells. AP-7 and pinostrobin had moderate selectivity, and 4-OHT had no selectivity. The best equations on QSPR analysis were ΔG = -0.003 TPSA² + 0.413 TPSA - 0.081 RM - 14.923; Ki = 4.609 Log P² - 24.089 Log P - 1.506 RM + 181.491; and %HIA = 0.491 Log P² - 3.041 Log P + 0.129 RM - 0.043 BM + 103.601. QSAR analysis showed that the best equation was not found. Therefore, it concluded that the 5 derivatives of 5-O- acylpinostrobin can be used as anti-breast cancer, which further can be in vivo studies

Keywords: Anti-breast cancer, 5-O-acylpinostrobin, cytotoxic, QSAR