Study of Structure Activity Correlation of 7-O-Amide Hesperetine Derivative based on Descriptor Calculation by Using AM1 as Anti-Inflammatory Candidate

Abstract

This study aims to study the quantitative relationship between molecular structure and biological activity (QSAR) of the 7-O-amide hesperetine derivative compounds and to design new compounds which are more potential as anti-inflammatory. This research was theoretically exploratory by using computational chemical methods. The object of this research was 23 derivative compounds of 7-O-Amide Hesperetine with their anti-inflammatory biological activity (IC50) values. The research data were obtained from the results of quantum chemistry calculations assist with computational chemistry code and statistical analysis of multiple linear regressions. The QSAR equation obtained was log IC50 = -2581,151 + (3127,454 × qC2) + (1884,436 × qC3) + (-1581,855 × qC11) + (8181,049 × qC8) + (-2166,325 ×qC4), where n = 23, R2 = 0.679, SEE = 0.092, Fcount /Ftable = 7189, and PRESS = 0.144. The best QSAR model was used to design and predict 23 new anti-inflammatory compounds of derived from 7-O-amide hesperetine with higher activity. The calculation results showed that the proposed anti-inflammatory compound with the highest activity to prevent inflammation was (S)-5-hydroxy-2-(3hidroxy-4-methoxyphenyl)-7-(2-oxo-2-(piperazine-1-yl)ethoxy )chroman-4-one (compound 38) with an IC50 value of 1.194 or 15.66 nM.