Current Topics in Medicinal Chemistry - Volume 23, Issue 2, 2023

Alzheimer’s Disease (AD) is a complex and progressive neurodegenerative disease, and the most common cause of dementia usually occurs due to old age. Production and accumulation of amyloid-β peptide (Aβ) represent the major pathological event of the disease. The formation of amyloid- β results due to proteolytic cleavage of amyloid precursor protein (APP) by beta-site amyloid precursor protein cleaving enzyme (BACE1) shown as the amyloid hypothesis, a prevalent theory for AD pathogenesis. Thus, BACE1 represents a novel target to decrease cerebral Aβ concentration and slow down the disease’s progression. The structure-based drug design approach led to a wide variety of small molecules with the mechanism of action centered around inhibition of β-secretase protease (BACE1), which are shown to have drug-like properties and reduce brain Aβ levels. Based on transition state isosteres, BACE1 inhibitors can largely be classified as peptidomimetics and non-peptidomimetics. The subclasses of the two categories have been covered with different scaffolds like statin, norstatin, carbinamine, hydroxyethylene, hydroxyethylamine, acyl guanidine, 2- aminopyridine, aminoimidazole, aminohydantoin, aminothiazoline, aminooxazoline, aminoquinoline, piperazine-based. Among these small molecules, those who fulfilled general requirements for a drug aimed at the central nervous system (CNS) and selectivity over other aspartyl proteases reached the final pipeline of clinical trials. Here, in this review, we summarize the journey of BACE1 inhibitors through different practices of drug design development, Structural Activity Relationship (SAR), and other inhibitor candidates that are currently in clinical trials as BACE1 inhibitors.

Pyridoxine and its derivatives, pyridoxamine, and pyridoxal have been recognized for more than 70 years and are known for regulating cellular biology and metabolism. During the past few decades, the anti-oxidant and anti-inflammatory properties of pyridoxine and its vitamers were explored. However, an interesting turnabout was observed in pyridoxine chemical modification in the last two decades. The various important pathophysiological aspects of pyridoxine and its derivatives on several cellular systems have been discovered by researchers. Recent findings have shown that many diseases, like cancer, diabetes, hypertension, tuberculosis, epilepsy, and neurodegenerative diseases are linked to the alteration of pyridoxine. Herein, our main focus is to review the importance of pyridoxine and its derivatives obtained by various chemical modifications, in various disease areas and to recognize important directions for future research.

Since late 2019, the novel coronavirus (COVID-19) pandemic has caused considerable mortality worldwide. This pandemic raised concerns and provoked research on the diagnosis and treatment of viruses-based diseases. The accurate diagnosis of a virus requires high specificity and sensitivity. Piezoelectric sensors are analytical devices that work on mass-sensitivity-based micromechanical transducers. The change in the mass by the interaction between biological elements and the frequency is recorded by measuring the alternate current and voltage. In addition to diagnosis, antiviral intervention strategies for mitigating various viral diseases are required. Nanomaterialsbased antiviral therapy is efficient, particularly with carbon/metal/metal oxide (organic/inorganic) nanoparticles. Metal/metal oxide nanoparticles, such as gold (Au), silver (Ag), copper (Cu), selenium (Se), zinc oxide (ZnO), magnesium oxide (MgO), carbon dots (CDs), and carbon quantum dots (CQDs), are promising candidates for antiviral therapy. This review discusses the piezoelectric sensors used to detect various viruses, including COVID-19, and the various organic and inorganic nanoparticles involved in the antiviral therapy.

Coronavirus disease (COVID-19) is the greatest pandemic of this era and has affected more than 10 million people across 213 nations. However, the etiology, management, and treatment of COVID-19 remain unknown. A better understanding of the novel virus would help in developing accurate diagnostic methods and efficacious drugs for the treatment of patients of all age groups. To control the pandemic urgently, many drugs are being repurposed and several clinical trials are in progress for the same. As cytokine storm has been observed to be one of the common mechanisms of immune response in COVID-19 patients, several drugs are under trials to control the cytokine storm. In this review, we discuss the different categories of drugs in clinical trials for the management of cytokine storms in COVID-19 patients. Hitherto, several promising candidates such as IL-1 and IL-6 inhibitors have failed to display efficacy in the trials. Only corticosteroid therapy has shown benefit so far, albeit limited to patients on ventilator support. Thus, it is crucial to seek novel strategies to combat hyperinflammation and increase survival in COVID-19 afflicted patients.

The COVID-19 virus caused countless significant alterations in the human race, the most challenging of which was respiratory and neurological disorders. Several studies were conducted to find a robust therapy for the virus, which led to a slew of additional health issues. This study aims to understand the changes in the neurological system brought about by COVID-19 drugs and highlights the drug-drug interaction between COVID-19 drugs and psychiatric drugs. Alongside this, the study focuses on the neuropsychological changes in three critical mental disorders, such as schizophrenia, Alzheimer’s disease, and Parkinson’s disease. The comprehensive and narrative review being performed in this paper, has brought together the relevant work done on the association of COVID-19 drugs and changes in the neurological system. For this study, a systematic search was performed on several databases such as PubMed, Scopus, and Web of Science. This study also consolidates shreds of evidence about the challenges confronted by patients having disorders like Schizophrenia, Alzheimer’s disease, and Parkinson's disease. This review is based on the studies done on COVID-19 drugs from mid-2020 to date. We have identified some scopes of crucial future opportunities which could add more depth to the current knowledge on the association of COVID- 19 drugs and the changes in the neurological system. This study may present scope for future work to investigate the pathophysiological changes of these disorders due to COVID-19.