In Silico Study of Novel Sulfonamide Derivatives Bearing a 1, 2, 4-Triazole Moiety Act as Carbonic Anhydrase Inhibitors With Promising Anti-Cancer Activity

Abstract

Aim: To evaluate the theoretical binding affinities of four synthetic compounds that target the carbonic anhydrase IX enzyme in solid tumors. Materials and Methods: To accurately depict the molecular structure, we utilized the Chem Draw Professional 12.0 program. We downloaded the carbonic anhydrase IX enzyme (29.25 KDa) (PDB code: 4YWP) from the Protein Data Bank into the Molecular Operating Environment software. Then, the S-score and rmsd were calculated for the proposed compounds. Results: The theoretically synthesized compounds demonstrated good binding affinities with the receptor active pockets Sa, Sb, and Sd, with S-scores of -7.6491, -8.3789, and -8.3218, respectively. Substitutions improve compound orientation. The substituted triazoles ring increases flexibility and receptor interaction. In addition, the benzyl chloride derivatives play an important role in the interaction, with varying effects dependent on the groups substituted at position 4 of the benzene ring. Conclusions: The synthesized compounds Sb with para Br substitution (S-score = -8.37) and Sd with para Cl substitution (S-score = -8.32) are considered the best ones as they exhibit a high affinity for the receptor.