Current Enzyme Inhibition - Volume 20, Issue 2, 2024

Glucagon-like peptide-1 and Glucose-dependent insulinotropic polypeptides are the most investigated gut peptides concerned with the biological glucose milieu. Early and late metabolism of incretin governs glucose homeostasis in diabetes mellitus. Dipeptidyl Peptidase-4, present in pancreatic alpha cells, is responsible for incretin degradation. Emerging biotechnological and molecular approaches established the pathophysiological role of Dipeptidyl Peptidase-4 and incretin in type 2 diabetes mellitus. Thus, various conventional synthetic Dipeptidyl Peptidase-4 inhibitors have been formulated, but they have serious adverse effects such as cancer, pancreatitis, cardiovascular risks, hepatic dysfunctions, etc. So, the concoction of a Dipeptidyl Peptidase-4 inhibitor entity with less or no severe adverse event becomes a need for society and medical corridor. Over the last two decades, natural or conventional herbal remedies have emerged as an alternate therapy for diabetes and treating its complications. This review summarized various plants (Emblica officinalis, Adenia viridiflora, Cleome droserifolia, Lens culinaris, Hedera nepalensis Melicope glabra, etc.) Dipeptidyl Peptidase-4 inhibitors, which have been preclinically proven for hyperglycemia treatment.

Enzyme inhibition is a crucial pharmacological approach for treating various diseases as it targets enzymes involved in disease pathogenesis. This review explores the fundamental concepts of enzyme inhibition, including reversible and irreversible mechanisms, and the various types of enzymes, such as proteases, kinases, and polymerases, and their contributions to different disease states. The review discusses the design and production of enzyme inhibitors using methods like structurebased drug design, high-throughput screening, and rational drug design. The review also discusses the challenges and successes encountered in discovering and optimizing potent and selective enzyme inhibitors. Examples of enzyme inhibition's therapeutic benefits include protease inhibitors in HIV/AIDS therapy, kinase inhibitors in cancer treatment, and acetylcholinesterase inhibitors in Alzheimer's disease management. The review also examines possible side effects and limits of enzyme inhibition, focusing on ways to reduce off-target effects and make drugs more specific. At the end of the review, new trends and future possibilities in enzyme inhibition for treating diseases are talked about. These include personalized medicine, combination therapies, and new ways to get drugs into the body. By shedding light on the latest developments, challenges, and future directions, the review aims to contribute to the advancement of this vital field and revolutionize disease treatment modalities.

Enzyme inhibition stands as a crucial strategy in tackling cardiovascular diseases (CVDs), countering their significant global impact on health. Targeting key enzymes involved in critical disease pathways has emerged as a pivotal pharmacological approach across various cardiovascular conditions. In hypertension, ACE inhibitors effectively lower blood pressure by impeding the conversion of angiotensin I to angiotensin II, promoting vasodilation and reducing cardiac workload. CAD management often involves statins, which competitively inhibit 3-hydroxy-3-methylglutarylcoenzyme A reductase, thereby lowering cholesterol levels and curbing plaque formation in coronary arteries. For heart failure, neprilysin inhibitors combined with ARBs exhibit promise by preserving beneficial peptides, supporting heart function and regulating fluid balance. Aspirin, an irreversible COX enzyme inhibitor, reduces platelet aggregation, mitigating thromboxane A2 formation and lowering the risk of clot-related complications in atherosclerosis. Managing dyslipidemia involves drugs like ezetimibe, targeting cholesterol absorption in the intestines and reducing LDL cholesterol levels. However, administering these drugs mandates careful consideration of patient-specific factors, potential side effects, and contraindications. Integrating lifestyle changes, such as a healthy diet and regular exercise remains integral to CVD management. The potential of enzyme inhibition in disrupting disease pathways and addressing key factors in CVD progression is evident. Yet, it necessitates ongoing research for refining existing therapies and developing novel inhibitors to augment cardiovascular outcomes and elevate patients' quality of life.

Background: Hyperpigmentation is a growing problem worldwide among various skin diseases and directly relates to the quality of life. The factors causing hyperpigmentation may range from excess exposure to sunlight, pollution, underlying disease conditions, adverse effects of a medication, modified lifestyle, and oxidative stress. Treatment includes the use of hydroquinone, retinoids, corticosteroids, and kojic acid along with anti-inflammatory drugs. However, these medications are preferred for short-term treatment under acute conditions, while in the case of long-term treatment, botanical extracts are a safe choice for a majority of the population for the treatment of hyperpigmentation. Formulation with plant extracts/oil enriched with polyphenols, vitamin C, and vitamin E are reported to be safe and effective in inhibiting melanogenesis. Objective: Seed oils composed of polyphenols, vitamins and unsaturated fatty acids were selected to evaluate their antioxidant property and tyrosinase enzyme inhibitory activity. Methods: Grape seed oil (GSO), papaya seed oil (PSO), and carrot seed oil (CSO) were evaluated for their total phenolic and flavonoid content,in-vitro antioxidant activity was done using DPPH assay and anti-tyrosinase activity was done using Mushroom tyrosinase inhibition assay. Results: Total phenolic content for PSO was 0.936 mg/gm. Gallic acid equivalent (GAE) was highest when compared to GSO and CSO, while CSO had a higher total flavonoid concentration, 0.945 mg/gm as quercetin equivalent (QE). Free radical scavenging activity was comparable to standard and tyrosinase inhibitory activity for grape and carrot seed oils were 80.10 % and 76.52 % at 100μg/ml, respectively and was comparable to kojic acid used as standard. Conclusion: The results obtained suggest that the oils can be formulated as a topical depigmenting product and used for skin care and skin glow.

Introduction: Recent studies have shown modified cyclobutene derivatives as potent anti- tubercular agents, and the discovery of drugs against strains of Mycobacterium tuberculosis is still a crucial challenge in the modern world. Objective: The objective of the present study is to design and perform molecular docking studies and in-silico analysis of some novel cyclobut-3-ene-1,2 Dione derivatives with the aim of creating new, potential Mtb ATP synthase inhibitors. Materials and Methods: The structures of 24 compounds of diamino-substituted cyclobut-3-ene-1,2 Dione derivatives against Mtb ATP synthase were drawn using ChemSketch. Further, molecular docking and in-silico studies for the prediction of drug-likeness and pharmacokinetic parameters were carried out. Results: The docking studies of the novel compounds were done, and they had a better docking score with a good binding affinity towards the protein molecule. The synthesized compounds also comply with the in-silico prediction of drug-likeness and pharmacokinetic parameters and have shown good activity against Mtb ATP synthase. Conclusion: The current study shows that the cyclobut-3-ene-1,2 Dione derivatives can serve as a better lead molecule against Mtb ATP synthase and can be involved in further drug discovery.

Background: To search for antifungal bioactive molecules from Ocimum sanctum, we used a molecular docking approach to identify the natural compound responsible for the property with a specific target. Our goal is to identify the potential antifungal compounds based on computational screening from reported chemical constituents of Tulsi as potential inhibitors of 14α- demethylase. Methods: Molecular docking was performed using Molergo Virtual docker software and validated based on the Root Mean Square Deviation (RMSD) value. Results: The compounds were docked to the pocket of the enzyme, and the docking results depicted that only oxygenated compounds were important for an antifungal profile with a good docking score and interaction with the enzyme molecule. Conclusion: The results suggest the availability of significant compounds with high potential for antifungal properties from O. sanctum. This suggests isolating these compounds for further lead identification to develop new antifungal compounds with specific targets.