Discovery of sulfadrug–pyrrole conjugates as carbonic anhydrase and acetylcholinesterase inhibitors

Abstract

Human carbonic anhydrase (hCA) isoenzymes are zinc ion‐containing, widespread metalloenzymes and they classically play a role in pH homeostasis maintenance. CA inhibitors suppress the CA activity and their usage has been clinically established as antiglaucoma agents, antiepileptics, diuretics, and in some other disorders. Alzheimer's disease (AD) is a slowly progressive neurodegenerative disorder and a fatal disease of the brain. An advanced method to cure AD includes the strategy to design acetylcholinesterase (AChE) inhibitors. A novel series of pyrrole‐3‐one derivatives containing sulfa drugs (5a–i) were determined to be highly potent inhibitors for AChE and hCA I and hCA II (inhibitory constant [Ki] values are in the range of 6.50 ± 1.02–37.46 ± 4.12 nM, 1.20 ± 0.19–44.21 ± 1.09 nM, and 8.93 ± 1.58–46.86 ± 8.41 nM for AChE, hCA I, and hCA II, respectively). The designed compounds often show a more effective inhibition than the chemicals used as the standard. Among these compounds, 5f was the most effective compound against hCA I, and compound 5e was the most effective compound against hCA II. It was determined that compound 5c was the most effective inhibitor for AChE.

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

“…3. Recently, compound bearing pyrrole-sulfonyl amine was reported as an example of pyrrole derivatives with IC 50 values ranging from 6.50 to 37.46 nm against AChE 63 .…”

Methyl benzoate derivatives: in vitro Paraoxonase 1 inhibition and in silico studies

“…[ 54–56 ] Plotting activity versus inhibitors yielded the half maximal inhibitory concentration values, inhibitory doses limiting enzyme activity by 50%. [ 57–59 ] To get K I constants and inhibition types, [ 60–63 ] three different inhibitory doses were used, as stated in earlier investigations. [ 64–67 ]…”

“…[54][55][56] Plotting activity versus inhibitors yielded the half maximal inhibitory concentration values, inhibitory doses limiting enzyme activity by 50%. [57][58][59] To get K I constants and inhibition types, [60][61][62][63] three different inhibitory doses were used, as stated in earlier investigations. [64][65][66][67] The fit of enzyme inhibition models was compared using the extra sumof-squares F test and the Akaike's corrected Information Criterion approach.…”

Screening of in vitro and in silico effect of Fluorophenylthiourea compounds on glucose 6‐phosphate dehydrogenase and 6‐phosphogluconate dehydrogenase enzymes

“…G6PD and 6PGD enzymes were purified from waste human blood erythrocytes using 2′‐5'‐ADP Sepharose 4B affinity chromatography as previously described 25‐27 . The protein content in the samples was determined by the Bradford method at 595 nm 28‐32 . To control enzyme purity, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) was used 33‐35 .…”