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The importance of new effective treatment methodologies for human immunodeficiency virus (HIV) is undeniable for the medical society. Viral protein U (Vpu), one of the disparaged accessory proteins of HIV, is responsible for the dissemination of viral particles, and HIV mutants lacking Vpu protein have remarkably reduced pathogenicity. Here, we explored the marine natural products to find the leading structures which can potentially inhibit the activity of Vpu in silico. To fulfill this goal, we set up a virtual screening based on molecular docking to evaluate the binding capacity of different marine products to Vpu. For validation, we used molecular dynamics simulation and monitored the root mean square deviation value and binding interactions. The results were intriguing when we realized that the hit compounds (phlorotannins) had previously been identified as reverse transcriptase and HIV protease inhibitors. This research inaugurates a new road to combat HIV by multifaceted mode of action of these marine natural products without putting the normal cells in jeopardy (with their safe toxicological profile). [ABSTRACT FROM AUTHOR]

In December 2019, a cluster of pneumonia caused by a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei province, China. Cytokine storm is an uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines and chemokines that occurs at phase 3 of viral infection. Such emergence led to the development of many clinical trials to discover efficient drugs and therapeutic protocols to fight with this single-stranded RNA virus. Corticosteroids suppress inflammation of the lungs during the cytokine storm, weaken immune responses, and inhibit the elimination of pathogen. For this reason, in COVID-19 corticosteroid therapy, systemic inhibition of inflammation is observed with a wide range of side effects. The present review discusses the effectiveness of the corticosteroid application in COVID-19 infection and the related side effects of these agents. In summary, a number of corticosteroids, including and especially methylprednisolone and dexamethasone, have demonstrated remarkable efficacy, particularly for COVID-19 patients who underwent mechanical ventilation. [ABSTRACT FROM AUTHOR]

Cancer remains a formidable global healthcare challenge, driving relentless research efforts. Among the diverse compounds explored for their potential in combating cancer, α,β‐unsaturated compounds have exhibited intriguing biological activities, including anticancer properties. In this study, we embarked on synthesizing novel α,β‐unsaturated compounds anchored by a phenylacrylonitrile base using the Knoevenagel reaction. Our investigation delved into the cytotoxicity of these compounds, where two standouts, 3 f and 3 g, demonstrated remarkable antiproliferative efficacy comparable to the established chemotherapy drug, doxorubicin, when tested against various cancer cell lines. Additionally, the influence of these compounds was evident as DNA fragmentation became apparent after a mere 24‐hour exposure. Molecular docking analysis unveiled a compelling interaction between our synthesized compounds and the P38‐α receptor, a pivotal player in the Mitogen‐Activated Protein (MAP) kinase 14 pathway. This revelation suggests the potential of our compounds to target this receptor, opening new avenues for further exploration. Our research not only underscores the promising anticancer potential of these α,β‐unsaturated compounds but also identifies a specific molecular target, P38‐α, paving the way for future investigations in cancer therapeutics. In an ever‐evolving quest to combat cancer, this study contributes valuable insights that may hold the key to innovative treatment strategies. [ABSTRACT FROM AUTHOR]

• A parallel three and five-component reactions are introduced between dimedone, aryl aldehydes, and 1-naphthylamine. • An unprecedented five-component route to the synthesis of bis(2-benzyl-5,5-dimethylcyclohexane-1,3-dione)-N- and 4- disubstituted naphthylamine derivatives is explored. • Some novel acridine derivatives are presented. • In-silico approaches such as target prediction, molecular modeling, and estimated values of pharmacokinetic factors of synthesized derivatives are investigated. A series of one-pot, atom-economic, in parallel three and five-component reactions for the synthesis of acridine and bis(2-benzyl-5,5-dimethylcyclohexane-1,3-dione)-N- and 4- disubstituted naphthylamine derivatives under green conditions from the reaction between dimedone, aryl aldehydes, and 1-naphthylamine have been investigated. The three-component route to the synthesis of acridine derivatives is well-known, but the five component route results in bis(2-benzyl-5,5-dimethylcyclohexane-1,3-dione)-N- and 4- disubstituted naphthylamine derivatives, which is an unprecedented pathway and is reported herein for the first time. By this achievement, a broad range of novel acridine and bis(2-benzyl-5,5-dimethylcyclohexane-1,3-dione)-N- and 4- disubstituted naphthylamine derivatives have been synthesized with substantial scores during in silico analyses, including molecular docking, molecular dynamics, and ADMET prediction tools. Acridine derivatives and N ,4-disubstituted naphthylamines appear to interact significantly with 5-HT 2A/C and MAO-A/B, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

The neuroscience and neurobiology of gene editing to enhance learning and memory is of paramount interest to the scientific community. The advancements of CRISPR system have created avenues to treat neurological disorders by means of versatile modalities varying from expression to suppression of genes and proteins. Neurodegenerative disorders have also been attributed to non-canonical DNA secondary structures by affecting neuron activity through controlling gene expression, nucleosome shape, transcription, translation, replication, and recombination. Changing DNA regulatory elements which could contribute to the fate and function of neurons are thoroughly discussed in this review. This study presents the ability of CRISPR system to boost learning power and memory, treat or cure genetically-based neurological disorders, and alleviate psychiatric diseases by altering the activity and the irritability of the neurons at the synaptic cleft through DNA manipulation, and also, epigenetic modifications using Cas9. We explore and examine how each different OMIC techniques can come useful when altering DNA sequences. Such insight into the underlying relationship between OMICs and cellular behaviors leads us to better neurological and psychiatric therapeutics by intelligently designing and utilizing the CRISPR/Cas9 technology. [ABSTRACT FROM AUTHOR]