Structural Modifications on Chalcone Framework for Developing New Class of Cholinesterase Inhibitors.

Due to the multifaceted pharmacological activities of chalcones, these scaffolds have been considered one of the most privileged frameworks in the drug discovery process. Structurally, chalcones are α, ß-unsaturated carbonyl functionalities with two aryl or heteroaryl units. Amongst the numerous pharmacological activities explored for chalcone derivatives, the development of novel chalcone analogs for the treatment of Alzheimer's disease (AD) is among the research topics of most interest. Chalcones possess numerous advantages, such as smaller molecular size, opportunities for further structural modification thereby altering the physicochemical properties, cost-effectiveness, and convenient synthetic methodology. The present review highlights the recent evidence of chalcones as a privileged structure in AD drug development processes. Different classes of chalcone-derived analogs are summarized for the easy understanding of the previously reported analogs as well as the importance of certain functionalities in exhibiting cholinesterase inhibition. In this way, this review will shed light on the medicinal chemistry fraternity for the design and development of novel promising chalcone candidates for the treatment of AD.

Current Perspective of COVID-19 on Neurology: A Mechanistic Insight.

SARS-CoV-2, the novel coronavirus and the causative organism of the Covid-19 pandemic wreaked havoc worldwide producing asymptomatic to symptomatic cases leading to significant morbidity and mortality even after infection. Most of the countries reported a mortality rate of 2-3 % majorly due to cardiorespiratory failures. Recent studies highlighted the neurological involvement playing a key role in cardiorespiratory failures and other symptoms such as headache, anosmia, and ageusia observed in Covid-19 patients. Studies suggest SARS-CoV-2 entry via Olfactory Epithelium (OE), and the expression of type 2 transmembrane serine protease (TMPRSS2) in addition to Angiotensin-Converting Enzyme 2 (ACE2) can facilitate SARS-CoV-2 neurotropism. The virus can either travel via peripheral blood vessel causing endothelial dysfunction, triggering coagulation cascade and multiple organ dysfunction or reach the systemic circulation and take a different route to the Blood-Brain Barrier (BBB), disrupting the BBB causing neuroinflammation or neuronal excitotoxicity resulting in the development of encephalitis, encephalopathy, seizures, and strokes. SARS-CoV-2 invasion on the brain stem is believed to be responsible for the cardiorespiratory failures observed in Covid-19 patients. Apart from viral invasion via hematogenous route, SARS-CoV-2 neural invasion via PNS nerve terminal, results in viral replication and retrograde transportation to soma leading to invasion of the CNS including the brain producing neurological manifestations of the disease either in the initial stages or during the course of the disease and even for a long period post-infection in many cases. The ACE2 receptors are expressed in the brain and glial cells and SARS-CoV-2 acts via neuronal as well as nonneuronal pathways. But the exact cell types involved and how they can trigger inflammatory pathways need further in-depth study for the development of targeted therapy.