Hansch Analysis of benzoxazole derivatives as 5-lipoxygenase inhibitors

Abstract

A QSAR study on benzoxazole derivatives as 5-lipoxygenase inhibitory agents was performed with 14 (11 training + 3 test) compounds. Molecular modeling studies were performed using Chemoffice 6.0 supplied by cambridgesoft. The sketched structures were subjected to energy minimization and the lowest energy structure was used to calculate the physiochemical properties. The regression analysis was carried out using a computer program called VALSTAT. The best models were selected from the various statistically significant equations. The substitution on benzoxazole ring affected the 5- LOX inhibition. The introduction of nitro group on 5-position of benzoxazole clearly decreased the activity (2e < 2b). However, 5 chloro benzoxazoles 2c and 2d showed almost same activity compared to their 5-H congeners 2a and 2b. The electron donating groups, such as 5- methyl and 5-methoxy, increased the activity (2f > 2a, 2g > 2b, and 2k > 2a). This observation could be explained by the proposed affinity of 5-LOX iron to the ligands having the enhanced electron density as a result of the introduction of electron donating X and Y to the aromatic rings. The analysis resulted in QSAR equation, which suggests that, n=9, r=0.923, r2=0.852, adjusted squared multiple R=0.711, Standard error of estimate(s) = 0.192 & validated r2 (q2) =0.631. This study can help in rational drug design and synthesis of new selective 5-lipoxygenase inhibitor with predetermined affinity.