"Synthesis and In Silico Analysis of Chalcone Derivatives as Potential Prostaglandin Synthetase Inhibitors"

Nine derivatives of chalcones were successfully synthesized using the Claisen-Schmidt condensation reaction between different derivatives of benzaldehyde and acetophenone at low temperature in the presence of potassium hydroxide (KOH) and ethanol.The compounds were obtained in high yield.The percentage yield ranges from 90.38 -27.68%, with sample B having the highest yield while sample I gave lowest yield.Also, the infra-red and nuclear magnetic resonance (FTIR and NMR) spectroscopic analysis shows distinct spectrum across all molecules, indicating the presence of unique functional groups and chemical environments.All the synthesized chalcones derivatives showed appreciable protein binding affinity against the COX-1 and COX-2 enzymes.The synthesized compounds had higher binding affinity against the COX-1 protein, compared to diclofenac and celecoxib that were used as standards.Sample A showed the highest affinity (-7.24 kcal/mol), while E showed the lowest affinity at -6.11 kcal/mol, higher than diclofenac (-5.46 kcal/mol) and comparable to celecoxib (-6.19 kcal/mol).For COX-2, Celecoxib (selective COX-2 blocker) showed highest binding affinity of -10.55 kcal/mol, while the test compounds B had -8.84 (highest among the test samples) and I (-8.69 kcal/mol (lowest affinity), with diclofenac having -8.49kcal/mol respectively.Compounds E (4-methoxy-4,6-diphenyl-2-thiopyrimidine) and B (para-chlorochalcone) from previous studies, displayed remarkable anti-inflammatory in an in-vivo animal model analysis.B showed the highest affinity against COX-2 and very high affinity towards COX-1 protein compared to the standard molecules.This shows that with adequate physiochemical and structural modifications, these compounds could serve as potential lead compounds in analgesic and anti-inflammatory pharmacology.