DESIGN, SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF ANTI-TUBERCULAR AGENTS TARGETING DECAPRENYL PHOSPHORYL RIBOSE D EPIMERASE-2 AND METHOXY MYCOLIC ACID SYNTHASE-2

Dr. Ayyadurai Jerad Suresh*, Rajendran Kalaiselvi, Namachivayam Ramya, Parakkot Ramakrishnan Surya

ABSTRACT

Mycobacterium tuberculosis MTB, or TB (tubercle bacillus), also called Phthisis or Phthisis pulmonalis, is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Over the past 200 years, tuberculosis has been responsible for the death of over 100 million people. Moreover due to the emergence and reemergence of multi-drug resistant tuberculosis (MDR-TB), extremely - drug resistant tuberculosis (XDR-TB), totally -drug resistant tuberculosis (TDR-TB) and also because of the co-infection of TB with HIV there is an urgent need for new Anti-TB agents. Today hetero cyclic compounds have attained wide attention in the discovery of new drug candidates because of their diverse biological activity. Among these, Benzimidazole and Thiophene derivatives are reported as effective compounds for tuberculosis both with respect to their inhibitory activity and their favorable selectivity ratio. So compounds with the benzimidazole and thiophene nucleous were designed and docked against MTB enzyme decaprenyl phosphoryl ribose d-epimerase-2 and methoxy mycolic acid synthase-2 by using Argus lab® software. The screened molecules were synthesized by condensation method, purified by chromatographic techniques, characterized by various spectral analytical techniques and evaluated for in-vitro anti mycobacterial activity against tuberculosis H37RV strain by Microplate Alamar Blue Assay (MABA) method. The experimental results show that Compound R2 possesses anti-tubercular activity with an MIC below 25 mcg/mL while R1, K 1, K2 showed moderate anti tubercular activity with an MIC below 50mcg/mL.

Keywords: Benzimidazole, Thiophene, Docking, MABA.