Mini Reviews in Medicinal Chemistry - Volume 24, Issue 17, 2024

Pain is characterized by the unpleasant sensory and emotional sensation associated with actual or potential tissue damage, whereas nociception refers to the mechanism by which noxious stimuli are transmitted from the periphery to the CNS. The main drugs used to treat pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics, which have side effects that limit their use. Therefore, in the search for new drugs with potential antinociceptive effects, essential oils have been studied, whose constituents (monoterpenes) are emerging as a new therapeutic possibility. Among them, linalool and its metabolites stand out. The present study aims to investigate the antinociceptive potential of linalool and its metabolites through a screening using an in silico approach. Molecular docking was used to evaluate possible interactions with important targets involved in antinociceptive activity, such as α2-adrenergic, GABAergic, muscarinic, opioid, adenosinergic, transient potential, and glutamatergic receptors. The compounds in the investigated series obtained negative energies for all enzymes, representing satisfactory interactions with the targets and highlighting the multi-target potential of the L4 metabolite. Linalool and its metabolites have a high likelihood of modulatory activity against the targets involved in nociception and are potential candidates for future drugs.

Diabetes is a rapidly growing health challenge and epidemic in many developing countries, including India. India, being the diabetes capital of the world, has the dubious dual distinction of being the leading nations for both undernutrition and overnutrition. Diabetes prevalence has increased in both rural and urban areas, affected the younger population and increased the risk of complications and economic burden. These alarming statistics ring an alarm bell to achieve glycemic targets in the affected population in order to decrease diabetes-related morbidity and mortality. In the recent years, diabetes pathophysiology has been extended from an ominous triad through octet and dirty dozen etc. There is a new scope to target multiple pathways at the molecular level to achieve a better glycemic target and further prevent micro- and macrovascular complications. Mitochondrial dysfunction has a pivotal role in both β-cell failure and insulin resistance. Hence, targeting this molecular pathway may help with both insulin secretion and peripheral tissue sensitization to insulin. Imeglimin is the latest addition to our anti-diabetic armamentarium. As imeglimin targets, this root cause of defective energy metabolism and insulin resistance makes it a new add-on therapy in different diabetic regimes to achieve the proper glycemic targets. Its good tolerability and efficacy profiles in recent studies shows a new ray of hope in the journey to curtail diabetes-related morbidity.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. AD patients usually present symptoms, such as cognitive dysfunction, progressive memory loss, and other manifestations. With the increasing number of AD cases worldwide, there is an urgent need to develop effective drug treatments. Currently, drugs targeting AD symptoms may not change or prevent the progression of the disease. Curcumin, a polyphenol extracted from the turmeric herb, has been used for the treatment of AD. In this review, we summarized both cellular and animal studies and described the mechanism of action of curcumin in altering the pathological features of AD. Curcumin attenuates the formation of amyloid-β plaques and promotes its decomposition, reduces the phosphorylation of tau, improves its clearance rate, and binds with copper to reduce cholesterol. It changes the activity of microglia, suppresses acetylcholinesterase, regulates insulin signal transduction, and exhibits antioxidant properties. Studies have found that curcumin can promote nerve repair and has a significant effect on AD. However, the low bioavailability of curcumin may hinder its use as a therapeutic agent. If this limitation can be overcome, curcumin may emerge as a promising drug for the treatment of AD.

Out of a variety of heterocycles, triazole scaffolds have been shown to play a significant part in a wide array of biological functions. Many drug compounds containing a triazole moiety with important antimicrobial, anticancer and antidepressant properties have been commercialized. In addition, the triazole scaffold exhibits remarkable antiviral activity either incorporated into nucleoside analogs or non-nucleosides. Many synthetic techniques have been produced by scientists around the world as a result of their wide-ranging biological function. In this review, we have tried to summarize new synthetic methods produced by diverse research groups as well as provide a comprehensive description of the function of [1,2,4] and [1,2,3]-triazole derivatives as antiviral agents. Antiviral triazole compounds have been shown to target a wide variety of molecular proteins. In addition, several strains of viruses, including the human immunodeficiency virus, SARS virus, hepatitis B and C viruses, influenza virus, Hantavirus, and herpes virus, were discovered to be susceptible to triazole derivatives. This review article covered the reports for antiviral activity of both 1,2,3- and 1,2,4-triazole moieties up to 2022.