38775-52-9Relevant academic research and scientific papers
Macrocyclic sulfone derivatives: Synthesis, characterization, in vitro biological evaluation and molecular docking
Ibrahim, Muhammad,Latif, Abdul,Ammara,Ali, Akbar,Ribeiro, Alany Ingrid,Farooq, Umar,Ullah, Farhat,Khan, Ajmal,Al-Harrasi, Ahmed,Ahmad, Manzoor,Ali, Mumtaz
, p. 562 - 574 (2021)
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 μM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC50 score of 55.3 ± 0.54 μM. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC50 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.
Sulfonylbis(acylhydrazones) as anticholinesterase inhibitors: Synthesis, in vitro biological evaluation and computational studies
Ahmad, Manzoor,Ahmad, Sajjad,Akbar, Nazia,Al-Harrasi, Ahmed,Ali, Akbar,Ali, Mumtaz,Ibrahim, Muhamad,Khan, Ajmal,Latif, Abdul,Saadiq, Mohammad,Siddique, Abu Bakar,farooq, Umar
, (2022/01/03)
This current research work is focused on the synthesis of sulfonyl-mediated hydrazones, its exploration as anticholinesterase inhibitors, in vitro biological evaluation, and computational studies. A series of 21 novel bis(acylhydrazones) (4a-u) have been synthesized in good to excellent yields using 4,4?-sulfonyldiphenol as the precursor. Characterization of the synthesized compounds was achieved via spectroscopic techniques i.e. UV, FT-IR, NMR (1H and 13C), and HRMS. In vitro anticholinesterase activity of these compounds was performed using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as cholinesterase enzymes. Among all the compounds tested, compounds 4 g and 4 h were found to be the most significant AChE inhibitions with IC50 values of 101.4 and 102.7 μM as compared to the standard cholinesterase inhibitor i.e., galantamine (IC50 = 104.5 μM). Additionally, compound 4 g was also found to be an excellent inhibitor of BChE with an IC50 value of 136.0 μM as compared to the standard galantamine (IC50 = 156.8 μM). Molecular docking of the most active compounds 4 g and 4 h also supported their potential to interact with cholinesterase enzymes. Further affirmation on the intermolecular stability of the docked complexes was achieved by molecular dynamics simulation for 100 ns with mean deviations ～2 ?. Residue level fluctuations analysis also interpreted the good stability of compounds interacting pocket residues. Lastly, binding free energy analysis was performed that decipher the intermolecular interactions that are dominated by both van der Waals and electrostatic energies. In short, both theoretical and experimental studies unveiled the compounds as potent blockers of cholinesterase enzymes.
