Synthesis of novel bis‐sulfone derivatives and their inhibition properties on some metabolic enzymes including carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase

Abstract

In this study, a series of novel bis-sulfone compounds (2a-2j) were synthesized by oxidation of the bis-sulfides under mild reaction conditions. The bis-sulfone derivatives were characterized by 1 H-NMR, 13 C-NMR, Fourier-transform infrared spectroscopy, and elemental analysis techniques. Nuclear Overhauser effect experiments were performed to determine the orientation of the sulfonyl groups in bis-sulfone derivatives. Here, we report the synthesis and testing of novel bis-sulfone compound-based hybrid scaffold of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the development of novel molecules toward the therapy of Alzheimer's disease. The novel synthesized bis-sulfone compounds demonstrated K i values between 11.4 ± 3.4 and 70.7 ± 23.2 nM on human carbonic anhydrase I isozyme (hCA I), 28.7 ± 6.6 to 77.6 ± 5.6 nM on human carbonic anhydrase II isozyme (hCA II), 18.7 ± 2.61 to 95.4 ± 25.52 nM on AChE, and 9.5 ± 2.1 to 95.5 ± 1.2 nM on BChE enzymes. The results showed that novel bissulfone derivatives can have promising drug potential for glaucoma, leukemia, epilepsy, and Alzheimer's disease, which are associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes. K E Y W O R D S acetylcholinesterase, bis-sulfide, butyrylcholinesterase, bis-sulfone, carbonic anhydrase

Plant‐mediated effects on life history traits of entomovirus infected caterpillars ofSpodoptera exigua

“…To defend against both the invasion of entomoviruses and the toxicity of secondary metabolites of plants, the metabolic systems of herbivores might develop a series of defensive strategies involving changing or activating the activities of their detoxifying and metabolic enzymes (Bier et al., 2019; Rane et al., 2016). Carboxylesterase (CarE) is an important detoxification enzyme of insects, which hydrolyses ester bonds or binds to lipophilic compounds (Yang et al, 2013).…”

Exploration of Some Bis‐Sulfide and Bis‐Sulfone Derivatives as Non‐Classical Aldose Reductase İnhibitors

“…Bis‐sulfide ( 5 a – i ) and bis‐sulfone ( 6 a – i ) derivatives were synthesized according to our previous studies [55,56] . We used bis‐chalcone derivatives in the synthesis of these compounds (Scheme 1).…”

“…In the light of all this information, this bis-sulfide (5 a-i) and bis-sulfone (6 a-i) derivatives, previously reported to have potent inhibitory activity versus some carbonic anhydrase isoforms (hCA I and hCA II) and cholinesterases (AChE and BChE), [55,56] was evaluated as non-classical ALR2Is against the pure ALR2 that was isolated from sheep kidney tissue. All derivatives (5 a-i and 6 a-i) are typically proven to exhibit activity against ALR2 with micromolar level concentrations, according to the in vitro and in silico inhibitory evaluation utilizing EPR as a positive standard.…”

“…[75] By reacting 1,4-Michael addition of bis-chalcones with thiophenol, we were able to synthesize bis-sulfides (5 a-i) using our previous methods. [56] At room temperature and under straightforward reaction conditions, bis-sulfides (5 a-i) were changed into bissulfones (6 a-i) by the employment of the oxidant meta-chloroperbenzoic acid (m-CPBA) (Scheme 1). [55] Spectroscopic details of the compounds are given in both this literature and Supplementary Information.…”

Synthesis, characterization, molecular docking, and biological activities of coumarin–1,2,3‐triazole‐acetamide hybrid derivatives

“…So, CA isoforms, which are involved in these processes, are important therapeutic targets with their inhibition potential to treat a range of disorders including glaucoma, edema, obesity, cancer, osteoporosis, and epilepsy. [ 14–16 ]…”