In Silico Design, Synthesis, And Quantitative Structure-Anti-Inflammatory Activity Relationships Of 5-O-Benzoylpinostrobin Analogs
To develop pinostrobin as a more potent anti-inflammatory, this study conducted a rational drug design by modifying the structure of the OH group of pinostrobin, which is esterified with benzoyl chloride analogs. The first step of this research is to conduct an in silico study and Quantitative Structure-Property Relationship (QSPR) of 20 analog compounds of 5-O-benzoylpinostrobin as an anti-inflammatory (inhibition of COX-2 enzyme). 5 compounds were selected that were predicted to have high activity and low toxicity to be synthesized. The results of the purity test showed that the TLC and melting point test results of five analogs of 5-O-benzoyl pinostrobin were pure. From the FTIR results, it is known that a C=O ester group is not owned in pinostrobin and the loss of the -OH group at C5 in pinostrobin. In the 1H-NMR spectrum of five synthetic 5-O-benzoyl pinostrobin analogs, no protons were found in the OH group of pinostrobin; there is also an additional H atom from the substituted benzoyl group. The results of the interpretation of the 13C-NMR spectrum of the synthetic 5-O-benzoyl pinostrobin analog compounds show that there is an additional C atom in the five synthetic 5-O-benzoyl pinostrobin analogs, which indicates that there is a C=O ester group, and there is also an additional C atom from the substituted benzoyl group. The LC-HRMS results of five synthetic 5-O- benzoyl pinostrobin analog compounds showed MW values that were within the theoretical MW values of the five test compounds. Furthermore, the five synthetic compounds were tested for anti- inflammatory activity in vivo in mice (Mus musculus). All synthetic 5-O- benzoyl pinostrobin analog compounds showed significant differences from the negative control (CMC-Na 0.5%). Meanwhile, the compound 5- O-(2,4-dichlorobenzoyl) pinostrobin dose of 30 mg/KgBW has better anti-inflammatory activity than the positive control (celecoxib). The Quantitative Structure-Activity Relationship (QSAR) study was conducted to find the physicochemical properties that play a role in its anti-inflammatory activity in experimental mice (Mus musculus). From the HKSA results, the best equation of all doses was obtained, namely %Inh = -0.001Etot - 73.988 (n = 5; r = 0.943; SE = 1.919; F = 24.143; sig.= 0.016).
Keywords: Analogs of 5-O-Benzoyl pinostrobin, Anti-inflammatory, Cyclooxygenase, Pinostrobin
