Macrocyclic sulfone derivatives: Synthesis, characterization, in vitro biological evaluation and molecular docking

An artificial series of macrocycles based on 4,4 '-sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide, etherification of phenolic hydroxyl groups, and final ring closure with different diamines. Different chemical species having aromatic, heteroaromatic, and aliphatic characters were incorporated into macrocyclic frameworks in the final step of ring closure. This simple and easily executable synthetic strategy was applied to synthesize 15 macrocycles (5a-o) in excellent yields. Characterization of the synthesized products was achieved through well-known modern spectroscopic techniques such as IR, NMR, and Mass. Macrocycles 5m and 5n were found to show significant AChE inhibition with IC50 values of 76.9 +/- 0.24 and 71.2 +/- 0.77 mu M, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC50 score of 55.3 +/- 0.54 mu M. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC50 value of 81.1 +/- 0.54 mu M. Increasing interest in studying interactions of macrocycles with different enzymatic targets compelled us to design and synthesize sulfone-based macrocycles that might prove as highly potent class of biologically active compounds.

Automated summary

A series of artificial macrocycles based on a 4,4'-sulfonyldiphenol intermediate were successfully synthesized through a multistep procedure involving oxidation, etherification, and ring closure, yielding 15 macrocycles characterized through modern spectroscopic techniques. Some of these macrocycles demonstrated significant AChE and BChE inhibition, highlighting their potential importance in studying interactions with various enzymatic targets.