Focus on chirality of HIV-​1 non-​nucleoside reverse transcriptase inhibitors

Chiral HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are of great interest since one enantiomer is often more potent than the corresponding counterpart against the HIV-1 wild type (WT) and the HIV-1 drug resistant mutant strains. This review exemplifies the various studies made to investigate the effect of chirality on the antiretroviral activity of top HIV-1 NNRTI compounds, such as nevirapine (NVP), efavirenz (EFV), alkynyl- and alkenylquinazolinone DuPont compounds (DPC), diarylpyrimidine (DAPY), dihydroalkyloxybenzyloxopyrimidine (DABO), phenethylthiazolylthiourea (PETT), indolylarylsulfone (IAS), arylphosphoindole (API) and trifluoromethylated indole (TFMI) The chiral separation, the enantiosynthesis, along with the biological properties of these HIV-1 NNRTIs, are discussed

Indolylarylsulfones, a fascinating story of highly potent human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors

Indolylarylsulfones are a potent class of human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors. In this review, the structure activity relationship (SAR) studies to improve the profile of sulfone L-737,126 discovered by Merck AG have been analysed with focus on introduction of the 3',5'-dimethyl groups at the 3-phenylsulfonyl moiety, the 2-hydroxyethyl tail at the indole-2-carboxamide nitrogen, coupling of the carboxamide nitrogen with one or two glycinamide and alaninamide units, a fluorine atom at position 4 of the indole ring and correlation between configuration of the asymmetric centre and linker length. IAS derivatives look like promising drug candidates for the treatment of AIDS and related infections in combination with other antiretroviral agents

Mitotic cell death induction by targeting the mitotic spindle with tubulin-inhibitory indole derivative molecules

Tubulin-targeting molecules are widely used cancer therapeutic agents. They inhibit microtubule-based structures, including the mitotic spindle, ultimately preventing cell division. The final fates of microtubule-inhibited cells are however often heterogeneous and difficult to predict. While recent work has provided insight into the cell response to inhibitors of microtubule dynamics (taxanes), the cell response to tubulin polymerization inhibitors remains less well characterized. Arylthioindoles (ATIs) are recently developed tubulin inhibitors. We previously identified ATI members that effectively inhibit tubulin polymerization in vitro and cancer cell growth in bulk cell viability assays. Here we characterise in depth the response of cancer cell lines to five selected ATIs. We find that all ATIs arrest mitotic progression, yet subsequently yield distinct cell fate profiles in time-lapse recording assays, indicating that molecules endowed with similar tubulin polymerization inhibitory activity in vitro can in fact display differential efficacy in living cells. Individual ATIs induce cytological phenotypes of increasing severity in terms of damage to the mitotic apparatus. That differentially triggers MCL-1 down-regulation and caspase-3 activation, and underlies the terminal fate of treated cells. Collectively, these results contribute to define the cell response to tubulin inhibitors and pinpoint potentially valuable molecules that can increase the molecular diversity of tubulin-targeting agents

Surveilling COVID-19 Emotional Contagion on Twitter by Sentiment Analysis

BACKGROUND: The fight against the COVID-19 pandemic seems to encompass a social media debate, possibly resulting in emotional contagion and the need for novel surveillance approaches. In the current study, we aimed to examine the flow and content of tweets, exploring the role of COVID-19 key events on the popular Twitter platform. METHODS: Using representative freely available data, we performed a focused, social media-based analysis to capture COVID-19 discussions on Twitter, considering sentiment and longitudinal trends between January 19 and March 3, 2020. Different populations of users were considered. Core discussions were explored measuring tweets’ sentiment, by both computing a polarity compound score with 95% Confidence Interval and using a transformer-based model, pretrained on a large corpus of COVID-19-related Tweets. Context-dependent meaning and emotion-specific features were considered. RESULTS: We gathered 3,308,476 tweets written in English. Since the first World Health Organization report (January 21), negative sentiment proportion of tweets gradually increased as expected, with amplifications following key events. Sentiment scores were increasingly negative among most active users. Tweets content and flow revealed an ongoing scenario in which the global emergency seems difficult to be emotionally managed, as shown by sentiment trajectories. CONCLUSIONS: Integrating social media like Twitter as essential surveillance tools in the management of the pandemic and its waves might actually represent a novel preventive approach to hinder emotional contagion, disseminating reliable information and nurturing trust. There is the need to monitor and sustain healthy behaviors as well as community supports also via social media-based preventive interventions

Groningen Identity Development Scale:Landscape version (GIDS-L)

The Groningen Identity Development Scale (GIDS-L2) is a semi-structured interview that comprehensively assesses an individual's identity in various domains of life, including occupation, family, friendships, relationships, leisure time, and a flexible domain. The GIDS-L2 employs a unique approach that combines domain-specific and integrative elements, allowing participants to formulate overarching commitments that tie their domain-specific commitments together into a coherent whole. Each domain interview involves three core questions about the individual's past, present, and future, resulting in a commitment statement specific to that domain. A questionnaire is then administered to assess the commitment's characteristics, such as strength and utility, and developmental processes that have shaped it, such as exploration and experiences. The GIDS-L2 is a unique tool for assessing identity that captures the qualitative distinctiveness of individuals while also providing quantitative metrics that facilitate comparisons between individuals

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes – NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases

DLLME PER L’ESTRAZIONE DI BDZ

È stato sviluppato un protocollo DLLME (Dispersive Liquid Micro Liquid Extraction) per la determinazione di 8 benzodiazepine (BDZ) in bevande. Sono stati ottimizzati volume e tipo dei solventi, forza ionica e uso di ultrasuoni ed il protocollo è stato validato ICH. I recuperi ottenuti di 14,30%-103,28% sono comparabili con la MEPS (Micro Extraction by Packed Sorbents) di 20,90%-101,88%