BIOACTIVE COMPOUNDS TO TARGET ANTI APOPTOTIC PROTEINS- Bcl 2 AND Bcl XL AN IN SILICO APPROACH

Phytochemicals from several herbaceous and spice plants have been reported to have defense properties against various diseases. Potential of some of such plants like Allium sativum, Curcuma longa, Boerhaavia diffusa, Pterocarpus marsupium and Zingiber officinale in cancer therapy has already been proved. The state of Kerala in southern India hosts large number of medicinal herbs and is also referred as a hotspot of biodiversity. The current study aimed at computational screening of potent lead molecules from ten selected medicinal plants and five spices widely used in Kerala, which are rich in biological diversity and its traditional values. Even though, the anticancer properties of all these plants and spices were reported, their mode of action and target molecules is not well explained. Hence, the interaction of these compounds with anti- apoptotic proteins Bcl-2 and Bcl-XL are studied and discussed in this paper. The - CDOCKER energy, - CDOCKER interaction energy, Hydrogen bonds, binding energy, and complex energy were predicted through molecular docking studies. Based on binding energy and CDOCKER scores, the active components of Pterocarpus marsupium, Aegle marmelos, Pseudarthira viscida, Allium sativum, Phyllanthus amarus, Boerhaavia diffusa and Catharanthus roseus were observed to have strong interaction with both the proteins. Pharmacokinetic analysis such as absorption, solubility, BBB penetration, and toxicity were also performed for these compounds. Comparative docking analysis showed higher interaction than the known inhibitors such as Obatoclax and apogossypolone. Finally, the lead molecules were screened based on their hepatotoxicity. Ten of them passed the analysis and some with high binding energy failed to do so. The lead molecules identified and their probable functional groups could be further reported to transform them as potential anti- apoptotic inhibitors.