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

Abstract

An artificial series of macrocycles based on 4,4 0 -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 IC 50 values of 76.9 ± 0.24 and 71.2 ± 0.77 μM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC 50 score of 55.3 ± 0.54 μM. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC 50 value of 81.1 ± 0.54 μM. 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.

One-Pot, Metal-Free Synthesis of Allyl Sulfones in Water

“…Sulfones are found in many important classes of natural products and biological molecules, − and the allyl sulfone moiety is known to have cysteine protease inhibitor, anticancer, antibacterial, and anti-inflammatory properties − and can also be used for dual site-specific labeling of proteins and cyclic peptides (Figure ). AMSO 2 , in particular, has been found to possess anti-inflammatory and antioxidant activity in a lung injury model induced by cigarette smoke extract (CSE) .…”