Role Organic Chemistry in Sciences

Chemistry and in particular Organic Chemistry plays a pivotal role in the field of Sciences to provide chemical compounds (molecules) for various studies of both academic interest and industrial importance. For example, new drugs, fertilizers, pesticides and insecticides, polymers and biopolymners, optoelectronic devices such as LCDs, LEDs, OLEDs etc. besides the latest development of nanomaterials all of them are originated from the development of new synthetic methods and methodologies to provide molecules of interest. In the field of new drug discovery, Organic Synthesis plays a significant role in providing desired molecules of potential biological interest although lot of challenges are not yet met for example in the discovery of suitable drugs with high efficiency and least side effects to treat ever increasing diseases such as cancer due to which millions of deaths are occurring annually throughout the world.

Heterocyclic compounds are needed in the area of medicinal chemistry and drug discovery thereby help to get insight into the function of biological systems.

The study of heterocyclic compounds also helps to generate biomarkers which have become very important nowadays in the field of drug discovery and development. It has been a great challenge for the chemists to discover suitable drugs to cure diseases such as cancer, heart disorders, arthritis, respiratory disorders etc. In the present proposal, I wish to work in ever demanding area of discovering new molecules for the treatment of cancer and similar diseases. It has been proven very well that heterocyclic compounds provide compatibility to biological systems particularly humans and hence several were brought out into the market successfully.

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Towards this end, I propose to work on the following series of molecules involving their design, synthesis, characterization, molecular docking studies, biological activity screening and finally profile building. The methodology involves the design of synthesis as shown below. The molecules thus synthesized would be characterized by spectral data such as 1HNMR, 13CNMR, IR, Mass, HRMS and elemental analysis. Crystallographic studies would be performed if necessary.

The well characterized compounds using spectral data are proposed to be subjected to a battery of biological activity/screening studies such as cytotoxicity, anti-cancer activity with a particular reference to programmed death ligand-1 [PD-L1] found on the surface of tumor cells, and programmed cell death protien-1 [PD-1] found on activated T and B cells and macrophages(Atezolizumab is the only member of this class currently approved for the treatment of bladder cancer).

 References:

1. Current treatments for the treatment of intermediate and advanced hepatocellular carcinoma, A.Vogel and A. Saborowski, Cancer treatment reviews, 82, 2020, 101946
2. A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer, The future is now, J. Bellmunt et.al., Cancer treatment reviews, 54(2017), 58-67
3. Discovery and biological evaluation – targeted chemotherapeutic agents for breast cancer, E.S. Lee et.al., Journal of Medicinal Chemistry, 2019, 62, 17, 8194-8234
4. Comprehensive in vitro characterization of PD-L1 small molecule inhibitors, Khaled Barakat et.al., Nature Scientific Reports, (2019) 9:12392