Research Projects

Marine natural products are important sources of biologically active agents and various bioactive compounds those were extracted from marine organisms like tunicates, sponges, soft corals, and molluscs. These biologically active compounds have been reported to modulate various biological activities and have anti-inflammatory, antifungal, and anticancer effects. Staurosporinone is the key starting material (KSM) for the synthesis of known marine derived drugs such as Midostaurin (PKC 412) which has been approved by FDA in 2017 to treat newly diagnosed AML that is FLT3 mutation positive. Many marine derived molecules, derivatives of staurosporinone [Lestaurtinib (CEP-701), CP-751, CEP-1347, Edotecarin and Becatecarin] are in phase-III/II clinical trials. The majority of the natural indolocarbazoles isolated to-date are derivatives of indolo[2,3-a]-pyrrolo[3,4-c]carbazole ring, which is the 7-keto derivative of staurosporinone. Due to the vast utility and applications staurosporinone and their analogues, the development of new methods for their synthesis is in high demand. Considering the uses of some of the staurosporinone based drugs for the mankind and in the medicinal field, the present proposal is aimed to develop the novel synthetic routes to access these scaffolds as described in the proposal. The present proposal builds on our recent studies on the synthesis of fused nitrogen-polycyclic heteroarenes and I propose herewith to undertake the synthesis of staurosporinone. In the present study, the staurosporinone could be obtained through transamidation such strategies have not been explored. After careful consideration of the above valid facts, the title research project appeared quite interesting and well justified for undertaking. Feasibility and successful execution of this project is based on the PI’s expertise in the synthesis of such heterocycles under various conditions. Potent drugs against cancer normally have to fulfil a number of requirements in terms of their toxicity to tumor cells and solubility for efficient delivery. This requires a full-fledged characterization of drug candidates, including possible synthetic strategies. The approved natural product derivatives may reduce the time required for their approval. In the present proposal, efforts will be made to concentrate on indolocarbazoles such as staurosporinone, the most potent and key starting material, as many derivatives could be made from this core structure once synthesised. Hence there is the need of synthetic routes to prepare indolocarbazole derivatives that are selective towards specific malfunctioning kinases associated with a disease.