Abstract

DESIGN, SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF FEW NOVEL DIAMINOPIMELATE DECARBOXYLASE INHIBITORS AS ANTI-TUBERCULAR AGENTS

Dr. Ayyadurai Jerad Suresh*, Rajendran Ravikumar, Parakkot Ramakrishnan Surya, Pooja J Patidar and Pooja K Patidar

ABSTRACT

Tuberculosis, an infectious disease is the most leading cause of death across the globe. Today, TB has became a burden to the world due to the emergence of “multi-drug resistant tuberculosis” (MDR-TB), “extremely drug resistant tuberculosis” (XDR-TB) and “totally drug resistant tuberculosis” (TDR-TB). This points to an urgent need for new promising drug candidates to combat the drug resistance and control the disease. Recent studies reveal the ability of Schiff bases to produce antibacterial, anti-tubercular anticancer and anti-inflammatory activity. Schiff bases are the compounds, containing the imine or azomethine (–C=N–) functional group. Hence, in the present research work a series of pyridine -3-carbohydrazide based Schiff bases were designed and docked against Mtb enzyme target Diaminopimelate decarboxylase. The molecules were screened based on the novelty, good docking-score and multiple interactions. The selected molecules were synthesized and repeatedly recrystallized to attain the expected purity. All the purified compounds were characterized by various spectral analytical techniques and evaluated for anti- mycobacterial activity against tuberculosis H37RV strain by Microplate Alamar Blue Assay (MABA) method. The experimental results shown that Compound (RK2) possesses anti-tubercular activity with an MIC below 3.12 mcg/mL while (RK2a, RK 3, RK 5, RK 7 and RK 9) showed moderate anti tubercular activity with an MIC below 50mcg/mL.

Keywords: Synthesis, Schiff base, Docking, MABA, Anti-tubercular.