Artificial neural network‐based drug design for diabetes mellitus using flavonoids

Abstract

Diabetes mellitus is a chronic metabolic disease involving the failure to regulate glucose blood levels in the body and has been linked with numerous detrimental complications. Studies have shown that these complications can be linked to the activities of aldose reductase (AR), an enzyme of the polyol pathway. Flavonoids have been identified as good AR inhibitors (ARIs) and are also strong antioxidants with radical scavenging (RS) activity. As such, flavonoids show potential to become a better class of ARIs because they are able to concurrently address the oxidative stress issue. In this article, we carried out quantitative structure-activity relationship analysis of flavones and flavonols (members of flavonoid family) using artificial neural networks. Three computer experiments were conducted to study the influence of hydrogen (H), hydroxyl (-OH), and methoxyl (-CH(3)) functional groups on eight substitution sites of the lead flavone molecule and to predict potential ARIs. Of 6561 possible flavones and flavonols, in experiment 1, we predicted 69 potent ARIs, and in experiment 2, we predicted 346 compounds with strong RS activity. In experiment 3, we combined these results to find overlapping compounds with both strong AR inhibition and RS activity and we are able to predict 10 potent compounds with strong AR inhibition (IC(50) < 0.3 μM) and RS activity (IC(25) < 1.0 μM). These 10 compounds show promise of being good therapeutic agents in the prevention of diabetic complications and is suggested to undergo further wet bench experimentation to prove their potency.

Machine Learning and Data Mining Methods in Diabetes Research

“…A QSAR model was also used to assess flavonoid inhibitory effects on AR activity as a potent treatment for diabetes, using artificial neural networks [120]. In [121], a novel method was proposed, based on association rule mining, to discover relationships between statin (reductase inhibitors, medication for cardiovascular disease) use and diabetes.…”

Influence of mulberry leaf extract on serum adiponectin, visfatin and lipid profile levels in type 2 diabetic rats

“…These compounds are abundant in fruits and vegetables and increasing evidence demonstrates a positive relationship between consumption of flavonoids-rich foods and disease prevention (8). As for as diabetes mellitus is concern, flavonoids play a vital role in all aspects and its mechanism is well known (9). Recent reports indicate that mulberry leaves and leaf-dried extracts are a rich source of polyphenol antioxidants, including phenolic acids and flavonoids, such as Caffeic acid, 5-Caffeoylquinic acid , Kaempferol (10).…”

QSAR study of some anti-hyperglycaemic sulphonylurea drugs

“…Other workers have modelled glitazones [5][6][7][8], spirohydantoins [9,10], PTP1B inhibitors [11] and flavonoids [12]. Murcia-Soler et al [4] also used molecular connectivities to model the acute toxicity (LD 50 ) *Corresponding author.…”