Mini Reviews in Medicinal Chemistry - Volume 24, Issue 20, 2024

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. With the increasing number of cases of diabetes and drug-resistant diabetes, there is an urgent need to develop new potent molecules capable of combating this cruel disease. Medicinal chemistry concerns the discovery, development, identification, and interpretation of the mode of action of biologically active compounds at the molecular level. Oxadiazole-based derivatives have come up as a potential option for antidiabetic drug research. Oxadiazole is a five-membered heterocyclic organic compound containing two nitrogen atoms and one oxygen atom in its ring. Oxadiazole hybrids have shown the ability to improve glucose tolerance, enhance insulin sensitivity, and reduce fasting blood glucose levels. The mechanisms underlying the antidiabetic effects of oxadiazole involve the modulation of molecular targets such as peroxisome proliferator-activated receptor gamma (PPARγ), α-glucosidase, α-amylase and GSK-3β which regulate glucose metabolism and insulin secretion. The present review article describes the chemical structure and properties of oxadiazoles and highlights the antidiabetic activity through action on different targets. The SAR for the oxadiazole hybrids has been discussed in this article, which will pave the way for the design and development of new 1,3,4-oxadiazole derivatives as promising antidiabetic agents in the future. We expect that this article will provide comprehensive knowledge and current innovation on oxadiazole derivatives with antidiabetic potential and will fulfil the needs of the scientific community in designing and developing efficacious antidiabetic agents.

Drug-like properties play pivotal roles in drug adsorption, distribution, metabolism, excretion, and toxicity. Therefore, efficiently optimizing these properties is essential for the successful development of novel therapeutics. Understanding the structure-property relationships of clinically approved drugs can provide valuable insights for drug design and optimization strategies. Among the new drugs approved in 2023, which include 31 small-molecule drugs in the US, the structure-property relationships of nine drugs were compiled from the medicinal chemistry literature, in which detailed information on pharmacokinetic and/or physicochemical properties was reported not only for the final drug but also for its key analogs generated during drug development. The structure-property relationships of nine newly approved drugs are summarized, including three kinase inhibitors and three G-protein-coupled receptor antagonists. Several optimization strategies, such as bioisosteric replacement and steric handle installation, have successfully produced clinical candidates with enhanced physicochemical and pharmacokinetic properties. The summarized structure-property relationships demonstrate how appropriate structural modifications can effectively improve overall drug-like properties. The ongoing exploration of structure-property relationships of clinically approved drugs is expected to offer valuable guidance for developing future drugs.

Background: The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage. Objective: The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles. Methods: The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer's Disease and Parkinson's Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study. Results: The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer's Disease and Parkinson's Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted. Conclusion: Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer's Disease and Parkinson's Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

Background: The National Health and Nutrition Examination Survey (NHANES) carried out a survey between 2007-10 and found that as compared to the general population, the prevalence of anemia in chronic kidney disease (CKD) patients was twice high. Daprodustat is an investigational novel drug for the treatment of renal anemia. Objective: The objective of this study is to provide a comprehensive review of chemistry, synthesis, pharmacology, pharmacokinetic, and bioanalytical methods for the analysis of Daprodustat. Methods: To improve understanding, a review was carried out by creating a database of relevant prior research from electronic sources such as ScienceDirect and PubMed. The methodology is shown in the flowchart of the literature selection process. Results: The drug was approved in 2020 for therapeutic purposes in Japan. It is a novel drug approved for the treatment of anemia in chronic kidney disease for oral administration. It is intended for adults who have undergone dialysis for a minimum of four months and are experiencing anemia as a result of chronic kidney disease. Conclusion: This review examines therapeutic, pharmacological, and analytical aspects related to the novel drug Daprodustat.

Skin is the largest organ of the human body functioning as a great primitive defensive barrier against different harmful environmental factors. However, it is damaged through varying injuries such as different wounds, burns, and skin cancers that cause disruption in internal organs and essential mechanisms of the body through inflammation, oxidation, coagulation problems, infection, etc. Melatonin is the major hormone of the pineal gland that is also effective in skin disorders due to strong antioxidant and anti-inflammatory features with additional desirable antiapoptotic, anti-cancer, and antibiotic properties. However, melatonin characteristics require improvements due to its limited water solubility, halflife and stability. The application of nanocarrier systems can improve its solubility, permeability, and efficiency, as well as inhibit its degradation and promote photostability. Our main purpose in the current review is to explore the possible role of melatonin and melatonin-containing nanocarriers in skin disorders focused on wounds. Additionally, melatonin's effect in regenerative medicine and its structures as a wound dressing in skin damage has been considered.