Background Inflammation is known to involve in many pathological processes of different diseases, but the current therapy causes adverse effects. Thus, there is a great interest for the discovery of flavonoids as a valuable alternative to classical analgesic and anti-inflammatory agent with dual-inhibitory action, especially on both COX-2 and 5-LOX which can minimize or overcome this problem. Results In the present work, drug-likeness properties of the synthesized flavonoids via Lipinski’s Rule of Five were predicted using QikProp prior to evaluation of their COX and LOX inhibitory activities using enzyme assays. Subsequently, molecular docking was performed using GLIDE to analyse their binding behaviour. The results showed that all compounds obeyed the Lipinski’s Rule of Five. NPC6 and NPC7 had displayed better selectivity towards COX-2 as compared to Indomethacin with less than 50% inhibition against COX-1. In addition, these compounds also inhibited activity of 5-LOX. Their selectivity to COX-2 was due to the binding to hydrophobic region and extends to lobby region near the entrance of COX binding site forming hydrogen bond with Ser530. Interestingly, these compounds showed a similar binding mode as Zileuton in the active site of 5-LOX and formed hydrogen bond interaction with Ala424. Conclusion NPC6 and NPC7 had potential as dual inhibitor of COX-2 and 5-LOX. The scaffolds of these chemical entities are useful to be as lead compounds for the dual inhibition of COX-2 and 5-LOX.

No abstract

Artocarpus odoratissimus is native to Borneo and Mindanao Island. In Sarawak, it is locally known as Terap. Previous studies showed Artocarpus species are rich in phenolic compounds, including flavonoids, stilbenoids and arylbenzofurons. The chemical profile of the indigenous plants from Sarawak, such as A. odoratissimus has not been studied intensively and the analyses of medicinal properties have not been explored. Thus, a phytochemical study is carried out on the root extracts of A. odoratissimus using various chromatographic methods and it has led to the isolation of two known flavonoids, namely pinocembrin (1) and pinostrobin (2). The structures are identified by comparison of their 1 H and 13 C NMR data with those reported in the literature. Flavonoid molecule incorporated as multifunctional in the pharmaceutical industry. It has a vast range of pharmacological activities, such as antimicrobial, anti-inflammatory, antioxidant, and anticancer activities. Pinocembrin and pinostrobin which are successfully synthesized with 2-hydroxy,4,6-methoxyacetphenone and benzaldehyde as starting materials were discussed.