Insilico Drug Design, Synthesis and Evaluation of Anti-inflammatory Activity Pyrimidine Analogue

ABSTRACT: A class of pyrimidine-based molecules was designed for their in silico study, synthesis, and testing for their in vitro anti-inflammatory evaluation. The compounds were tested in an in silico study against anti-inflammatory proteins like FAAH (PDB ID: 4DO3) by using two different software programmes, Ace-dock and Arguslab, and showed promising signs of being a possible drug candidate. In silico toxicity prediction was also done on these compounds. The drug-likeness screening was done to satisfy the Lipinsky rule of five. In our recent investigation, we focused on environment-friendly approaches to synthesising pyrimidine derivatives in the presence of an ethanolic potassium hydroxide solution. The Claisen-Schmidt condensation of acetophenone and various substituted benzaldehydes produces pyrimidine. The pyrimidine derivatives 2a-p and 3a-c were synthesized. The synthesised molecules were screened on the basis of an in silico study, and the molecules were selected and subjected to a check for their in vitro anti-inflammatory activity. A test called the albumin denaturation assay was used to see how much heat-induced protein denaturation could be stopped. The compounds that were synthesised and the standard drug, diclofenac sodium, both stopped protein denaturation at levels ranging from 100 to 500 ppm. Maximum inhibition of 68.59% was observed at the concentration of 100 ppm of compound 2d. Diclofenac sodium showed the maximum inhibition, which was 80.58% at a concentration of 100 ppm. It is concluded that 2d has the potential for further investigation for anti-inflammatory activity.