The enzyme phospholipase A2 is responsible for the hydrolysis of membrane phospholipids that release arachidonic acid, which serves as a substrate for pro-inflammatory mediators, such as prostaglandins and leucotriens. The binding of the substrate to PLA2 occurs through a well-formed hydrophobic channel. So blocking the hydrophobic channel is an effective way to inhibit PLA2. Compounds inhibiting PLA2 have been implicated as potential therapeutic agents in the treatment of inflammation related diseases. Curcumin is a well studied compound isolated from the plant Curcuma longa. The PLA2 inhibiting activity of curcumin has been studied in our laboratory. The present study focuses whether any of the curcumin analogs can bind PLA2 more strongly than curcumin. To check this, binding of twenty eight different curcumin analogs to PLA2 have been studied by molecular modeling and docking. The mode of interactions of compounds with strong binding are discussed and reported here. It has been observed that four analogs namely rosmarinic acid, tetrahydrocurcumin, dihydrocurucmin and hexahydrocurcumin possess better binding energy than curcumin. The present study may lead to the better understanding of PLA2 inhibition by curcumin analogs. This may help to develop better anti-inflammatory drugs.

Inhibition of acetylcholinesterase (AChE) is a promising treatment strategy for Alzheimer's disease (AD). Oxidative stress, inflammation and accumulation of metal ions at sites of neurodegeneration have been observed in association with AD. Flavonoids are well known for their action against inflammation and oxidative stress. Hence, they can be used for treating diseases such as AD, cancer, atherosclerosis and Parkinson's disease. Flavonols such as quercetin, myricetin, galangin, fisetin and kaempferol have been reported as inhibitors of AChE. In the present work, the enzyme inhibitory properties of morin, a flavonol, has been tested against AChE. The binding pattern of morin and 12 other flavonols at the active site of human AChE has been analyzed using molecular modeling and docking methods. In order to enhance the binding affinity of AChE for morin, in silico structural modification of the compound was carried out. The structural elements responsible for its biological functions were retained during the modification. Some of the derivatives possessed better binding energies than morin and hence they could be used as drug lead compound for the treatment of AD.

Inhibiting PLA 2 activity should, in theory, be an effective approach to control the inflammation. Several naturally occurring polyphenolic compounds have been reported as inhibitors of PLA 2 . Among the naturally occurring polyphenols, catechol (1,2-dihydroxybenzene) possesses antiinflammatory activity. Catechol can inhibit cyclooxygenase and lipo-oxygenase. By means of enzyme kinetic study, it was revealed that catechol can inhibit PLA 2 also. Crystal structure showed that catechol binds to PLA 2 at the opening of the active site cleft. This might stop the entry of substrate into the active site. Hence, catechol can be used as a lead compound for the development of novel anti-inflammatory drugs with PLA 2 as the target.

Acetylcholinesterase (AChE) inhibitors are currently in focus for the pharmacotherapy of Alzheimer's disease (AD). These inhibitors increase the level of acetylcholine in the brain and facilitate cholinergic neurotransmission. AChE inhibitors such as rivastigmine, galantamine, physostigmine and huperzine are obtained from plants, indicating that plants can serve as a potential source for novel AChE inhibitors. We have performed a virtual screening of diverse natural products with distinct chemical structure against AChE. NDGA was one among the top scored compounds and was selected for enzyme kinetic studies. The IC(50) of NDGA on AChE was 46.2 μM. However, NDGA showed very poor central nervous system (CNS) activity and blood-brain barrier (BBB) penetration. In silico structural modification on NDGA was carried out in order to obtain derivatives with better CNS activity as well as BBB penetration. The studies revealed that some of the designed compounds can be used as lead molecules for the development of drugs against AD.