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Identification of novel inhibitors of chorismate mutase enzyme involved in shikimate pathway of Mycobacterium tuberculosis: Design and in-vitro screening
3rd World Congress on Biotechnology
Reshma Chowdary Alokam, Jean kumar, D. Sriram and P.Yogeeswari
Tuberculosis is a frightful disease which affects one third of world population, and kills 1-2 million people a year, is a top health
priority. The emergence of multiple and extensively drug resistant forms (MDR and XDR) of the disease that are difficult to
treat with the existing drug regimen. Despite this need, no new drug classes have been specifically marketed for TB in the last forty
years, in part owing to lengthy and costly process that makes almost two decades for drug approval. One strategy that will allow
for a rapid path to new anti-TB agents to discover new classes of compounds against already validated targets. One of the target
is Chorismate mutase (E.C 5.4.99.5), which catalysis conversion of Chorismate to prephenate by claisen rearrangement. This
enzymatically catalysed conversion of Chorismate proceed through a endo-oxa bicyclic (chair- like) transition state. Chorismate
plays a key role in shikimate pathway for biosynthesis of aromatic amino acids like phenyl alanine, tyrosine and tryptophan. Thus,
it has a main role in maintaining the balance between these aromatic amino acids in the cell is vital. In this study, we performed
invitro screening of inhouse database molecules. More than 15 molecules showed IC50 below 1micro molar concentration. These
were further supported by docking studies using Glide module (schrodinger.Inc). Hence, the thiazine derivative which showed
highest percentage of inhibition at 1micromolar conccentration can be a potential lead for treating tuberculosis.
Biography
Reshma Chowdary Alokam completed her M.sc Microbiology from Avanthi PG College affiliated to Osmania University. Currently she is pursuing her
Ph.D from BITS-Pilani Hyderabad Campus, Jawahar Nagar, Hyderabad.
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