Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics is conferred by the enzymatic modification of the antibiotic. Therefore, a deeper knowledge of the aminoglycoside-modifying enzymes and their interactions with the antibiotics and solvent is of paramount importance in order to facilitate the design of more effective and potent inhibitors and/or novel semisynthetic aminoglycosides that are not susceptible to modifying enzymes.

Multidrug efflux systems play a prominent role in medicine, as they are important contributors to bacterial antibiotic resistance. NorA is an efflux pump transporter from the major facilitator superfamily that expels numerous drug compounds across the inner membrane of Staphylococcus aureus (S. aureus). The design of novel inhibitors to combat drug efflux could offer new opportunities to avoid the problem of antibiotic resistance. In this study, we performed molecular modeling studies in an effort to discover novel NorA efflux pump inhibitors. A group of over 673 compounds from the PubChem database with a high (>80%) level of similarity to the chemical structure of capsaicin was used to study the binding affinity of small molecule compounds for the NorA efflux pump. Ten potential lead compounds displayed a good druggability profile, with one in particular (CID 44330438) providing new insight into the molecular mechanism of the inhibition of major facilitator superfamily (MFS) efflux pump transporters. It is our hope that the overall strategy described in this study, and the structural information of the potential novel inhibitors thus identified, will stimulate others to pursue the development of better drugs to tackle multidrug resistance in S. aureus.

Chondroitin sulfates are linear anionic sulfated polysaccharides found in biological tissues, mainly within the extracellular matrix, which are degraded and altered by specific lyases depending on specific time points. These polysaccharides have recently acquired relevance in the pharmaceutical industry due to their interesting therapeutic applications. As a consequence, chondroitin sulfate (CS) lyases have been widely investigated as tools for the development of new pharmaceuticals based on these polysaccharides. This review focuses on the major breakthrough represented by chondroitin sulfate-degrading enzymes and their structures and mechanisms of function in addition to their major applications.

The guanidine functional group is an important structural motif in synthesis with a wide range of interesting properties. Guanidines are frequently found in bioactive compounds; both from natural sources or from synthetic origin, these compounds are considered fundamental entities in medicinal chemistry. The relevance of these compounds fosters the efforts to explore new methodologies for the synthesis of substances based on the guanidine core. The aim of this review is to provide a survey of the types of reactions used to prepare these classes of compounds. Given the vast number of contributions to this topic, we have focused on the achievements made in the last five years and, in particular, in the synthesis of biologically relevant heterocyclic guanidine-derivatives.

[Introducción]: La biorremediación es una tecnología que utiliza microorganismos (bacterias, hongos, algas) o enzimas, para biodegradar contaminantes del petróleo y derivados y como otros contaminantes que están presentes en suelo, aire o agua. En América Latina existe un alto grado de contaminación de sus ecosistemas; por tanto, esta tecnología es viable económica y ambientalmente para degradar contaminantes. Los hidrocarburos aromáticos policíclicos como asfaltenos y resinas son difíciles de degradar, así como los alifáticos y bifenilos policlorados. [Objetivo]: Se busca dar una visión general de las publicaciones recientes sobre investigaciones científicas realizadas, y metodologías de biorremediación de suelos contaminados por petróleo y sus derivados. [Metodología]: Se realizó una búsqueda exhaustiva de la literatura científica de los últimos años, relacionado al tema propuesto en bases de datos bibliográficas: Medline, Current Contents, PubMed, Google scholar, SciFinder, Scopus y en revistas especializadas: Chemosphere, Microbiología Aplicada, Biodegradation & Biodeterior, Sociedad Americana de Microbiología, Microbiología Frontal, Sci Total Environ. Las palabras clave utilizadas fueron en español o inglés. [Resultados]: Los hidrocarburos poliaromáticos pueden ser biodegradados por diferentes bacterias que biodegradan solas o en consorcio, como el fenantreno (compuesto aromático) que fue biodegradado por 11 cepas bacterianas diferentes (Sphingobium, Sphingomonas, Acidovorax, Alkaligenes, Actinobacteria, Burkholderia sp., Rhizobium sp., Pseudomonas sp., Stenotrophomonas y Sinorhizobium). En biorremediación se considera importante las variables fisicoquímicas, como el pH, temperatura, oxígeno y la humedad, al ser factores que influyen en el éxito del tratamiento. [Conclusiones]: Se buscó aportar con esta revisión, soluciones viables a variados problemas de contaminación por hidrocarburos de los ecosistemas latinoamericanos.

The pandemic associated to Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) has resulted in a huge number of deaths and infected people. Although several vaccine programmes are currently underway and have reached phase 3, and a few small size drugs repurposed to aid treatment of severe cases of COVID-19 infections, effective therapeutic options for this disease do not currently exist. NSP16 is a S-adenosyl-L-Methionine (SAM) dependent 2′O-Methyltransferase that converts mRNA cap-0 into cap-1 structure to prevent virus detection by cell innate immunity mechanisms. NSP16 methylates the ribose 2′O-position of the first nucleotide of the mRNA only in the presence of an interacting partner, the protein NSP10. This feature suggests that inhibition of the NSP16 may represent a therapeutic window to treat COVID-19. To test this idea, we performed comparative structural analyses of the NSP16 present in human coronaviruses and developed a sinefungin (SFG) similarity-based virtual screening campaign to assess the druggability of the SARS-CoV-2 NSP16 enzyme. Through these studies, we identified the SFG analogue 44601604 as a promising more potent inhibitor of NSP16 to limit viral replication in infected cells, favouring viral clearance.