Naturally occurring enzyme inhibitors and their pharmaceutical applications

Abstract

Enzyme inhibitors play a significant role in the drug discovery process. For instance, acetylcholinesterase (AChE) inhibitors have applications in curing Alzheimer's disease (AD), senile dementia, ataxia, myasthenia gravis, and Parkinson's disease. Glutathione S-transferase (GST) inhibitors have applications as adjuvants to overcome anticancer and antiparasitic drug resistance problems. Compounds inhibiting the activity of α-glucosidase are used to treat type 2 diabetes mellitus and obesity problems. This article describes the identification of natural products exhibiting AChE, GST, and α-glucosidase inhibitory activities from medicinally important plants. Additionally, structure-activity relationship (SAR) studies of these newly discovered enzyme inhibitors are also discussed.

Exploration of natural enzyme inhibitors with hypoglycemic potentials amongst Eucalyptus Spp. by in vitro assays

“…However, hyper or hypo activity of such enzymes leads to malfunctions of the respective biochemical processes which in many cases are the underlying causes of diseases like diabetes, Alzheimer's disease, myasthenia gravis and Parkinson's disease, as depicted by their etiopathogenesis at the molecular level. It is anticipated that enzyme inhibitors serve as important therapeutic targets for these diseases [5] . It has been found that enzymes like α-amylase, α-glucosidase, dipeptidyl peptidase 4 (DPP4), aldose reductase (AR), angiotensin converting enzyme (ACE) and peroxisome proliferator activated receptor-γ (PPAR-γ) contribute significantly to the pathogenesis of type 2DM.…”

“…Phytomolecules, as natural enzyme inhibitors (NEIs), can serve as successful therapeutic bullets in the control of this chronic disease [2,[5][6][7][8] . The World Health Organization has recommended phytotherapy for diabetes due to safety, effectivity, availability and affordability.…”

“…Inhibiting the actions of carbohydrate hydrolyzing enzymes like α-amylase and α-glucosidase helps to reduce post-prandial (PP) hyperglycemia. Inhibition of other enzymes like AR, DPP-4, ACE and PPAR-γ also presents an effective strategy to combat type 2 DM naturally [5,6,8,11] . Extensive literature surveys and our previous works have reported that Eucalyptus shows the presence of terpenoids, triterpenoids, flavonoids, polyphenols and tannins in its various volatile and non-volatile fractions [8,21,22] .…”

Bioactive steroidal alkaloids from Buxus macowanii Oliv.

“…The excessive degradation of acetylcholine by AChE results in its deficiency, which is reported to be associated with Alzheimer's disease (AD) [8,9]. The use of AChE inhibitors to enhance acetylcholine level in the brain is one of the most effective approaches to treat early symptoms of AD [8][9][10][11]. Four anti-AD drugs approved by the FDA namely, tacrine, donepezil, galantamine, and rivastigmine work by inhibiting the activity of AChE [12].…”

Novel Indole Alkaloids from Nauclea latifolia and Their Renin‐Inhibitory Activities

“…Its IR spectrum displayed intense absorption bands at 3283 (OH), 2922 (CH), and 1655 cm À 1 (amide C¼O). The (S)-configuration at C(3) in 5 was proposed based on the optical-rotation data and chemical-shift value as discussed for 4, and the configuration at the stereogenic center C (19) remains to be determined. 375.1583), was established by HR-EI-MS, which showed a molecular-ion peak at m/z 375.1579.…”