In Vitro Inhibitory Activity and Molecular Docking Study of Selected Natural Phenolic Compounds as AR and SDH Inhibitors**

Abstract

Polyol pathway enzymes, aldose reductase (EC 1.1.1.21; AR, ALR2), and sorbitol dehydrogenase (EC 1.1.1.14; SDH, SORD) have been widely investigated as the enzymes crucially involved in the pathogenesis of several chronic complications, including nephropathy, neuropathy, retinopathy, and cataracts associated with diabetes mellitus. Although phenolic compounds have been reported to possess many other biological activities, in continuation of our interest in designing and discovering potent inhibitors of AR and SDH, herein, we have evaluated these agents’ inhibitory potential against polyol pathway enzymes. Our in vitro studies revealed that all the derivatives show activity against recombinant human AR (rhAR) and SDH (rhSDH), with KI constants ranging from 9.37±0.16 μM to 77.22±2.49 μM and 2.51±0.10 μM to 42.16±1.03 μM, respectively. Among these agents, Prunetin and Phloridzin showed prominent inhibitory activity versus rhAR and rhSDH, while some were also determined to possess perfect dual activity. Moreover, in silico studies were also performed to rationalize binding site interactions of these agents with the target enzyme AR and SDH. According to ADME‐Tox was also determined that these derivatives be agents exhibiting suitable drug‐like properties. The compounds identified therapeutic potentials in this study may be promising for developing lead therapeutic agents to prevent polyol pathway complications.

Ornamental cabbage (Brassica oleracea var. acephala) responses to phytase enzyme purified from Lactobacillus coryniformis application

“…[13][14][15] Enzymes are produced by cellular anabolism, the naturally occurring biological process to make more complex molecules from simpler ones. 16,17 Agricultural enzymes can be defined as biocatalysts that accelerate chemical reactions by breaking down the nutrients in the soil to be easily absorbed by plant roots. Therefore, agricultural enzymes are bioactive proteins that help increase crop production, soil fertility, and food preservation.…”

Unveiling the Suppressive Potential of Phenolic Compounds on Bovine Milk Lactoperoxidase

“…In the literature, there are reported that some different phenolic compounds showed a significant inhibitory effect on aldose reductase (AR), sorbitol dehydrogenase (SDH) enzymes, 6‐phosphogluconate dehydrogenase (6PGD), glucose‐6‐phosphate dehydrogenase (G6PD), paroxanase‐1, carbonic anhydrase isozymes hCA I, and hCA II enzymes. Exemplarily, in a recent study, the effects of 4‐methylcatechol, danshensu, esculin, morin, naringin, phloridzin, prunetin, schizandrin, vanillic acid on AR and SDH were examined and it has been shown that these phenolic acids had strong inhibitory effects on activity of AR and SDH enzymes [17–18] . The effect of phenolic compounds on glucose‐6‐phosphate dehydrogenase and 6‐phosphogluconate dehydrogenase enzymes was investigated and it was observed that these compounds showed an inhibition effect at the μM level [19] …”

“…Exemplarily, in a recent study, the effects of 4-methylcatechol, danshensu, esculin, morin, naringin, phloridzin, prunetin, schizandrin, vanillic acid on AR and SDH were examined and it has been shown that these phenolic acids had strong inhibitory effects on activity of AR and SDH enzymes. [17][18] The effect of phenolic compounds on glucose-6-phosphate dehydrogenase and 6phosphogluconate dehydrogenase enzymes was investigated and it was observed that these compounds showed an inhibition effect at the μM level. [19] While phenolic compounds offer diverse health benefits, excessive intake can disrupt metabolic processes, potentially harming organisms.…”

Protective effect of bromelain on some metabolic enzyme activities in tyloxapol‐induced hyperlipidemic rats

“…14,15 There has been a noticeable rise in interest in plants recently, as well as the potential for employing natural chemicals derived from plants as medicines. 16,17 We are observing a global resurgence in interest in using botanical therapy and plants in healthcare products because of their significant efficacy in many fields of medicine with few high availability, side effects, and relative ease of acquisition. 18,19 Bromelain is a member of a class of proteolytic enzymes employed orally for the systemic treatment of bloodclotting-related illnesses, inflammation, and cancer.…”

“…Therefore, one of the core aims of contemporary pharmacology is the quest for novel physiologically active substances that can exert various effects with little toxicity 14,15 . There has been a noticeable rise in interest in plants recently, as well as the potential for employing natural chemicals derived from plants as medicines 16,17 . We are observing a global resurgence in interest in using botanical therapy and plants in healthcare products because of their significant efficacy in many fields of medicine with few high availability, side effects, and relative ease of acquisition 18,19 …”