MERIT OF INDOLE β-DIKETONATES AS SCAFFOLDS IN DRUG DISCOVERY-AN IN SILICO APPROACH USING DISCOVERY STUDIO

Abstract

From a medicinal chemist’s viewpoint, two scaffolds can be diverse, if they are built up via different synthetic routes. Synthetic curcumin is one of such scaffold studied and synthesized extensively in different part of word. Though many analogues were patented, major pitfalls in curcumin chemistry without a significant therapeutic agent requires attention. The existing multi directional studies in the last forty-plus years with diverse curcumin templates are to be analyzed to find out the most suitable scaffold among them. It is a high time to investigate, test and hypotheses in silico prior to costly random experimental implementation of synthetic curcumin. The diverse approach existed in SAR based synthesis and the existing numerous synthetic approaches should be streamlined for reducing the time and expense involved in bringing products to market. So, this study focuses on collection and in silico screening of existing templates of “curcumin research” for cyto toxicity receptor binding. It further continues with identification and enlightenment on highly disputed pharmacophore in curcumin, which is responsible for high potential cytotoxic action. The aim of curcumin scaffold hoping is to synthesis structurally novel compound from the identified templates by in silico method and to explore the core structures ability to bind with the most suitable receptor. The second part of work is on modifying synthetic route, which make it appropriate for synthesizing the series of compounds from most eligible drug candidate. At the same time, parallel to these acute toxicity studies of these sequences of compound was conducted in the aim of bringing a safe analogue. Curcumin research, which turned out to be one of the preferred subjects for organic, inorganic chemists should need a direction. By this scaffold hoping and in silico analysis on available synthetic analogues for a given target will definitely give light on ability of these diverse compounds to bind on same receptor. The in vivo and in vitro studies help in exploring the effect of modification on pharmacophore features of identified eligible drug candidate. Scaffold hopping will be an excellent method to be experimented in this juncture of curcumin research