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अमूर्त

Significance of Biotransformation in Drug Discovery and Development

Selvan Ravindran, Sudipta Basu, Prashant Surve, Ganesh Lonsane and Navya Sloka

Biotransformation is a process by which organic compounds are transformed from one form to another, aided by organisms such as bacteria, fungi and enzymes. Biotransformations are used as a valuable strategy to build molecules, similar to parent drug in the drug discovery programme. Biotransformations can also be used to synthesize compounds or materials, if synthetic approaches are challenging. Microbial biotransformations or microbial biotechnology are extensively used to generate metabolites in bulk amounts. Biotransformation approaches and synthetic methods in tandem provide a source for generating compounds around core structures, which can be screened for various biological activity studies. These studies help in screening and advancing the compounds, through various stages of drug discovery programme. Hence, biotransformation experiments can be effectively utilized to synthesize more compounds.

In the present study, a sulfonylurea urea drug was incubated with microsomal proteins to produce metabolites. Liquid chromatography is used to separate the formed metabolites and the parent drug. Fragmentation pattern obtained from the mass spectrum is utilized to identify the biotransformation site in the molecule, which is the metabolic soft spot. Identified new metabolites are structurally similar to parent drugs, implying the possibility of better therapeutic effects.

Few phase-I metabolites and phase-II metabolites are predicted with the help of liquid chromatography and mass spectrometry data. Synthesis of these identified, as well as predicted metabolites, and subjecting them to various pharmacological and toxicological studies will help to generate new materials with valuable therapeutic properties.