STRUCTURE-GUIDED SYNTHESIS AND EVALUATION OF N- (4-CETAMIDOPHENYL SULFONYL) - AMINO ACID CONJUGATES AS CARBONIC ANHYDRASE II INHIBITORS

Diksha Gawshindea, Darshana Shrivastavaa, Adnan Naimb, Mirza S. Baigb and Meena Tiwaria*

ABSTRACT

Carbonic anhydrases are important enzymes that catalyze interconversion of CO2 and water into bicarbonate. They
are crucial for maintaining pH homeostasis and water balance. Apart from this they are also involved in biological
processes like respiration, ureagenesis, gluconeogenesis etc. Inhibition of CA can produce a number of therapeutic
effects in the body. CA inhibitors are used in treatment of diseases like glaucoma, epilepsy, hypoxic tumors. Lack
of specificity, low potency and poor pharmacokinetic properties of the existing drugs suggests the need of new
inhibitors. In the present work N-(4-Acetamidophenyl sulfonyl)-Amino acid conjugates with carboxyl/amino end
were synthesized using acetanilide as starting material. Inhibition activity of these compounds was evaluated
against bovine CA II. Compound G13 showed highest inhibition (80.13%) comparable to the standard inhibitor
acetazolamide (78.91%) Docking studies were performed to study the amino acid interaction and the binding mode
of ligands within the active site.

Keywords: Carbonic anhydrase, amino acid, Acetazolamide, Inhibition, Docking