Biological activity and molecular docking studies of some N‐phenylsulfonamides against cholinesterases and carbonic anhydrase isoenzymes

Abstract

In this research, a series of N‐phenylsulfonamide derivatives (1‐12) were designed, synthesized, and investigated for their inhibitory potencies against carbonic anhydrase isoenzymes I, II, and IX (hCA I, hCA II, and hCA IX) and cholinesterases (ChE), namely, acetylcholinesterase and butyrylcholinesterase. These compounds, whose inhibition potentials were evaluated for the first time, were characterized by spectroscopic techniques (1H‐ and 13C‐NMR and FT‐IR). CA isoenzyme inhibitors are significant therapeutic targets, especially owing to their preventive/activation potential in the therapy processes of some diseases such as cancer, osteoporosis, and glaucoma. On the other hand, Cholinesterase inhibitors are valuable molecules with biological importance that can be employed in the therapy process of Alzheimer's patients. The results showed that the tested molecules had enzyme inhibition activities ranging from 9.7 to 93.7 nM against these five metabolic enzymes. Among the tested molecules, the methoxy and the hydroxyl group‐containing compounds 10, 11, and 12 exhibited more enzyme inhibition activities when compared to standard compounds acetazolamide, sulfapyridine, and sulfadiazine for CA isoenzymes and neostigmine for ChE, respectively. Of these three molecules, compound 12, which had a hydroxyl group in the para position in the aromatic ring, was determined to be the most active molecule against all enzymes. In silico work, molecular docking has also shown similar results and is consistent with the experimental data in the study. As a result, we can say that some of the tested molecules might be used as promising inhibitor candidates for further studies on this topic.

Synthesis of Novel Hydrazide–Hydrazone Compounds and In Vitro and In Silico Investigation of Their Biological Activities against AChE, BChE, and hCA I and II

“…AZA was used as a positive control compound. Notably, the study’s findings were represented through individual graphs delineating the activity percentages in relation to inhibitor concentrations, as elucidated by prior research sources. ,,, …”

“…AD is a progressive and fatal neurodegenerative disease characterized by impairment in the person’s ability to perform daily activities and cognitive dysfunction in the later stages of the disease. ,− AD is the most common cause of dementia seen in the elderly, accounting for an estimated 60–70% of cases worldwide. With aging of our world population, the prevalence of dementia would increase globally.…”

Synthesis, antioxidant, and anticholinesterase activities of novel N‐arylsulfonyl hydrazones bearing sulfonate ester scaffold

“…Alzheimer's disease (AD), which is a neurodegenerative disease, is an irreversible disease that first begins with the deterioration of the patient's ability to perform daily activities and is characterized by cognitive dysfunction and different neuropsychiatric symptoms in the later stages. [1][2][3][4] While the first symptom of AD is near memory impairment and forgetfulness, distant memory is preserved for a while. In the ongoing processes of the disease, a decrease in the patient's ability to use various objects is observed.…”

“…In addition, it was determined that the effect of treatment with memantine, an Nmethyl-D-aspartate receptor antagonist, and combined ChEIs increased. [4][5][6]8,9,11,12] . However, the need for new inhibitors for the treatment of this disease continues due to the insufficiency of existing ChEIs.…”

Some Novel Schiff Base Derivatives as Promising Cholinesterase Inhibitors With Antioxidant Activity Against Alzheimer’s Disease: Synthesis, Characterization and Biological Evaluation

“…Inadequate cholinergic transmission plays a significant role in the emergence of cognitive, functional, and behavioral symptoms in AD. Therefore, cholinesterase inhibitors (ChEIs) are used to increase the decreased amount of acetylcholine (ACh) in the brain in the cholinergic hypothesis [10,11]. This hypothesis is the only currently accepted hypothesis to explain the nature of this disease [12,13].…”