Premium
Macrocyclic sulfone derivatives: Synthesis, characterization, in vitro biological evaluation and molecular docking
Author(s) -
Ibrahim Muhammad,
Latif Abdul,
Ali Akbar,
Ribeiro Alany Ingrid,
Farooq Umar,
Ullah Farhat,
Khan Ajmal,
AlHarrasi Ahmed,
Ahmad Manzoor,
Ali Mumtaz
Publication year - 2021
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21775
Subject(s) - chemistry , sulfone , butyrylcholinesterase , combinatorial chemistry , proton nmr , phthalimide , ring (chemistry) , sulfoxide , stereochemistry , organic chemistry , enzyme , aché , acetylcholinesterase
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 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.