Antifungal Activity of Amphiphilic Perylene Bisimides

[EN] Perylene-based compounds, either naturally occurring or synthetic, have shown interesting biological activities. In this study, we report on the broad-spectrum antifungal properties of two lead amphiphilic perylene bisimides, compounds 4 and 5, which were synthesized from perylene-3,4,9,10-tetracarboxylic dianhydride by condensation with spermine and an ammonium salt formation. The antifungal activity was evaluated using a collection of fungal strains and clinical isolates from patients with onychomycosis or sporotrichosis. Both molecules displayed an interesting antifungal profile with MIC values in the range of 2-25 mu M, being as active as several reference drugs, even more potent in some particular strains. The ammonium trifluoroacetate salt 5 showed the highest activity with a MIC value of 2.1 mu M for all tested Candida spp., two Cryptococcus spp., two Fusarium spp., and one Neoscytalidium spp. strain. Therefore, these amphiphilic molecules with the perylene moiety and cationic ammonium side chains represent important structural features for the development of novel antifungals.This study was supported by grant 201680I008 (awarded to M.A.G.-C.) from the Spanish Government (Consejo Superior de Investigaciones Cientificas) and grant 3756 of the University of Antioquia.Roa-Linares, VC.; Mesa-Arango, AC.; Zaragoza, RJ.; González-Cardenete, MA. (2022). Antifungal Activity of Amphiphilic Perylene Bisimides. Molecules. 27(20):1-12. https://doi.org/10.3390/molecules27206890112272

Host Cell Targets for Unconventional Antivirals against RNA Viruses

The recent COVID-19 crisis has highlighted the importance of RNA-based viruses. The most prominent members of this group are SARS-CoV-2 (coronavirus), HIV (human immunodeficiency virus), EBOV (Ebola virus), DENV (dengue virus), HCV (hepatitis C virus), ZIKV (Zika virus), CHIKV (chikungunya virus), and influenza A virus. With the exception of retroviruses which produce reverse transcriptase, the majority of RNA viruses encode RNA-dependent RNA polymerases which do not include molecular proofreading tools, underlying the high mutation capacity of these viruses as they multiply in the host cells. Together with their ability to manipulate the immune system of the host in different ways, their high mutation frequency poses a challenge to develop effective and durable vaccination and/or treatments. Consequently, the use of antiviral targeting agents, while an important part of the therapeutic strategy against infection, may lead to the selection of drug-resistant variants. The crucial role of the host cell replicative and processing machinery is essential for the replicative cycle of the viruses and has driven attention to the potential use of drugs directed to the host machinery as therapeutic alternatives to treat viral infections. In this review, we discuss small molecules with antiviral effects that target cellular factors in different steps of the infectious cycle of many RNA viruses. We emphasize the repurposing of FDA-approved drugs with broad-spectrum antiviral activity. Finally, we postulate that the ferruginol analog (18-(phthalimide-2-yl) ferruginol) is a potential host-targeted antiviral

Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone

Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa and Jurkat tumor cell lines was also tested. Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells. NQ 4 showed a fair antiviral activity against Herpesviruses (EC50: <0.4 µg/mL, <1.28 µM) and DENV-2 (1.6 µg/mL, 5.1 µM) on pre-infective stages. Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC50: 0.12 µg/mL, 0.38 µM) with a very high selectivity index (SI = 1728). The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2. These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections. Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents

Uncovering the Resistome of a Peruvian City through a Metagenomic Analysis of Sewage Samples

Background: Antibiotic resistance is a major public health concern globally. In this study, we aimed to evaluate the abundance and diversity of antibiotic resistance genes (ARGs) in sewage water samples from two hospitals and an adjacent community or urban setting in Huanuco, a Peruvian city located in the highlands. Methods: We collected samples from the community wastewater system and from sewage pipes from the two hospitals in Huanuco. DNA was extracted from 250 mL of sewage water samples (n = 6) and subjected to microbiome profiling using 16S rRNA short amplicon sequencing and shotgun metagenomics. We analyzed the taxonomic and functional content in all samples, including alpha and beta diversity metrics, and searched for ARGs. Results: Our results showed that samples taken from the community wastewater system were compositionally different and harbored greater bacterial taxonomic and functional diversity compared to samples collected from the hospitals’ wastewater system. We found a high abundance of bacteria associated with resistance to beta-lactams, macrolides, aminoglycosides, fluoroquinolones, and tetracyclines in all samples. However, there were no significant differences in the abundance or composition of ARGs between the community wastewater samples and those taken from the two hospitals. Conclusions: Our findings suggest that metagenomics analyses in wastewater sewage could be a useful tool for monitoring antibiotic resistance in urban settings. These data could be used to develop local public health policies, particularly in cities or countries with limited resources to establish large-scale One Health projects