Synthesis of kanamycin-azole hybrids and investigation of their antifungal activities.

The World Health Organization (WHO) recognizes Candida albicans and Cryptococcus neoformans as the critical priority fungal pathogens for which therapeutic solutions are needed. Azole-based antifungal agents, including triazoles, diazoles, and thiazoles, are widely used in the treatments for fungal infections. In light of past successes in the transformation of antibacterial kanamycin into antifungal derivatives via chemical modifications, a new library of kanamycin-azole hybrids was synthesized and tested against a panel of azole-resistant and susceptible Candida and Cryptococcus strains.

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling.

DUSP22, an atypical dual-specificity phosphatase enzyme, plays a significant role in regulating multiple kinase signaling pathways by dephosphorylation. Our study demonstrated that decreased DUSP22 expression is associated with shorter disease-free survival, advanced TNM (tumor, lymph nodes, and metastasis), cancer stage, and higher tumor grade in lung adenocarcinoma (LUAD) patients. Exogenous DUSP22 expression reduces the colony-forming capacity of lung cancer cells and inhibits xenograft tumor growth primarily by targeting EGFR and suppressing its activity through dephosphorylation.

Binding Affinity, Selectivity, and Pharmacokinetics of the Oxytocin Receptor Antagonist L-368,899 in the Coyote ().

L-368,899 is a selective small-molecule oxytocin receptor (OXTR) antagonist originally developed in the 1990s to prevent preterm labor. Although its utility for that purpose was limited, L-368,899 is now one of the most commonly used drugs in animal research for the selective blockade of neural OXTR after peripheral delivery. A growing number of rodent and primate studies have used L-368,899 to evaluate whether certain behaviors are oxytocin dependent.

Mesobiliverdin IXα-enriched microalgae feed additive eliminates reliance on antibiotic tylosin to promote intestinal health of weaning piglets.

Weaning is a critical period in raising pigs. Novel animal feed additives that promote gut health and regulate immune function of piglets without antibiotics are needed. In this study, we aimed to test the ability of mesobiliverdin IXα-enriched microalgae (MBV IXα-enriched microalgae) to eliminate reliance on antibiotics to promote intestinal health in piglets.

KI04 an Aminoglycosides-Derived Molecule Acts as an Inhibitor of Human Connexin46 Hemichannels Expressed in HeLa Cells.

Background: Connexins (Cxs) are proteins that help cells to communicate with the extracellular media and with the cytoplasm of neighboring cells. Despite their importance in several human physiological and pathological conditions, their pharmacology is very poor. In the last decade, some molecules derived from aminoglycosides have been developed as inhibitors of Cxs hemichannels.

Amphiphilic aminoglycosides: Modifications that revive old natural product antibiotics.

Widely-used -derived antibacterial aminoglycosides have encountered challenges because of antibiotic resistance and toxicity. Today, they are largely relegated to medicinal topical applications. However, chemical modification to amphiphilic aminoglycosides can revive their efficacy against bacterial pathogens and expand their targets to other pathogenic microbes and disorders associated with hyperactive connexin hemichannels.

Mesobiliverdin IXα ameliorates osteoporosis via promoting osteogenic differentiation of mesenchymal stem cells.

Heme oxygenase-1 (HO-1) expression promotes osteogenesis, but the mechanisms remain unclear and therapeutic strategies using it to target bone disorders such as osteoporosis have not progressed. Mesobiliverdin IXα is a naturally occurring bilin analog of HO-1 catalytic product biliverdin IXα. Inclusion of mesobiliverdin IXα in the feed diet of ovariectomized osteoporotic mice was observed to increase femur bone volume, trabecular thickness and osteogenesis serum markers osteoprotegrin and osteocalcin and to decrease bone resorption serum markers cross-linked N-teleopeptide and tartrate-resistant acid phosphatase 5b.

A Glimpse into the Diverse Cellular Immunity against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response has been shown to play a critical role in preventing severe illness or death in patients infected with SARS-CoV-2 or its variants. Given the multiple T-cell epitopes shared by wild-type virus and its variants, we hypothesized that vaccines that target multiple T-cell epitopes of SARS-CoV-2 may provide a "universal protection" against the wild-type virus as well as its variants, even the heavily mutated ones. To test this, we assessed SARS-CoV-2-specific T-cell precursors in healthy individuals using overlapping peptide pools of SARS-CoV-2 structural and functional proteins, including spike (S), membrane (M), envelope (E), nucleocapsid (N), and protease (P) proteins as target antigens.

Connexin hemichannel inhibitors with a focus on aminoglycosides.

Connexins are membrane proteins involved directly in cell-to-cell communication through the formation of gap-junctional channels. These channels result from the head-to-head docking of two hemichannels, one from each of two adjacent cells. Undocked hemichannels are also present at the plasma membrane where they mediate the efflux of molecules that participate in autocrine and paracrine signaling, but abnormal increase in hemichannel activity can lead to cell damage in disorders such as cardiac infarct, stroke, deafness, cataracts, and skin diseases.

Effects of Mesobiliverdin IXα-Enriched Microalgae Feed on Gut Health and Microbiota of Broilers.

Gut inflammatory bowel diseases (IBDs) links to animal medicinal feed and antibiotic-resistance are fueling major economic impacts in the agricultural livestock industry. New animal feeds that promote livestock gut health and control of IBDs without antibiotics are needed. This study investigates the effects of mesobiliverdin IXα (MBV)-enriched microalgae spirulina extracts on the growth performance, blood parameters, intestinal morphology, and gut microbiota of broilers.

Amphiphilic aminoglycosides with increased selectivity for inhibition of connexin 43 (Cx43) hemichannels.

Gap junction channels formed by the association of connexin hemichannels play a crucial role in intercellular communication. Connexin 43 (Cx43) is expressed in a variety of tissues and organs, including heart and brain, and abnormal sustained opening of undocked "free" hemichannels contributes to the cell damage in cardiac infarcts and stroke. Selective inhibitors of Cx43 hemichannels for clinical use are then desirable.

Nanoconfinement of metal oxide MgO and ZnO in zeolitic imidazolate framework ZIF-8 for CO adsorption and regeneration.

Microporous materials exhibit fast CO adsorption rate with possible sacrificed capacity, while CO chemisorption on metal oxides is remarkable but kinetics and reactive area are critical. In order to adopt the advantages of both microporous sorbent zeolitic imidazolate framework (ZIF) and metal oxide (MO), in this research, magnesium oxide (MgO) and zinc oxide (ZnO) were doped to ZIF-8 (MO@ZIF) using infiltration and calcination processes. The powder X-ray diffraction patterns showed retained ZIF-8 integrity after MO addition.

DUSP22 suppresses prostate cancer proliferation by targeting the EGFR-AR axis.

Dual-specificity phosphatases (DUSPs) regulate the activity of various downstream kinases through serine or threonine or tyrosine dephosphorylation. Loss of function and aberrant expression of DUSPs has been implicated in cancer progression and poor survival, yet the function of DUSP22 in prostate cancer (PCa) cells is not clear. Gene Expression Omnibus and cBioPortal microarray database analyses showed that DUSP22 expression was lower in PCa tissues than normal prostate tissues, and altered DUSP22 expression was associated with shorter progression-free and disease-free survival of patients with PCa.

Scalable and cost-effective tosylation-mediated synthesis of antifungal and fungal diagnostic 6″-Modified amphiphilic kanamycins.

Amphiphilic kanamycins bearing hydrophobic modifications at the 6″ position have attracted interest due to remarkable antibacterial-to-antifungal switches in bioactivity. In this report, we investigate a hurdle that hinders practical applications of these amphiphilic kanamycins: a cost-effective synthesis that allows the incorporation of various connecting functionalities to which the hydrophobic moieties are connected to the kanamycin core. A cost-effective tosylation enables various modifications at the 6″ position, which is scalable to a 90-g scale.

Cationic Anthraquinone Analogs as Selective Antimicrobials.

Development of new antibiotics is always needed in the fight against growing threat from multiple drug-resistant bacteria, such as resistant Gram-negative (G-) and . While the development of broad-spectrum antibiotics has attracted great attention, careful administration of these antibiotics is important to avoid adverse effects, like infection (CDI). The use of broad-spectrum antibiotics, for example, quinolones, can increase the risk of CDI by eradicating the protective bacteria in intestine and encouraging spore germination.

Antifungal Activities of 4″,6″-Disubstituted Amphiphilic Kanamycins.

Amphiphilic kanamycins derived from the classic antibiotic kanamycin have attracted interest due to their novel bioactivities beyond inhibition of bacteria. In this study, the recently described 4″,6″-diaryl amphiphilic kanamycins reported as inhibitors of connexin were examined for their antifungal activities. Nearly all 4″,6″-diaryl amphiphilic kanamycins tested had antifungal activities comparable to those of 4″,6″-dialkyl amphiphilic kanamycins, reported previously against several fungal strains.

Development of Fungal Selective Amphiphilic Kanamycin: Cost-Effective Synthesis and Use of Fluorescent Analogs for Mode of Action Investigation.

Amphiphilic aminoglycosides have attracted interest due to their novel antifungal activities. A crucial but often neglected factor for drug development in academia is cost of production. Herein is reported a one-step, inexpensive synthesis of amphiphilic alkyl kanamycins constituted with only natural components.

Tuning the biological activity of cationic anthraquinone analogues specifically toward Staphylococcus aureus.

Development of new antibacterial agents against drug resistant bacteria is an imminent task, especially against methicillin-resistant Staphylococcus aureus (MRSA). While MRSA can still be treated with broad spectrum antibiotics, the use of which often leads to the disruption of normal microbial flora leading to Clostridium difficile infection (CDI). Herein, a new class of antibacterial agent, cationic anthraquinone analogues specifically against MRSA, has been developed.

Antifungal amphiphilic kanamycins: new life for an old drug.

Classical aminoglycoside antibiotics are obsolete or hampered by the emergence of drug resistant bacteria. Recent discoveries of antifungal amphiphilic kanamycins offer new strategies for reviving and repurposing these old drugs. A simple structural modification turns the clinically obsolete antibacterial kanamycin into an antifungal agent.

Synthesis and biological activity investigation of azole and quinone hybridized phosphonates.

Phosphonates, azoles and quinones are pharmacophores found in bioactive compounds. A series of phosphonates conjugated to azoles and quinones with variable carbon chain lengths were synthesized in 3-4 steps with good yield. Antifungal assay of these compounds showed that ethyl protected phosphates have excellent inhibitory activity against phytopathogenic fungus Fusarium graminearum, and the free-base phosphates have good activity against human pathogenic fungi Aspergillus flavus and Candida albicans.

Inhibition of Connexin Hemichannels by New Amphiphilic Aminoglycosides without Antibiotic Activity.

Connexins hemichannels (HCs) from adjacent cells form gap junctional channels that mediate cell-to-cell communication. Abnormal opening of "free" undocked HCs can produce cell damage and participate in the mechanism of disorders such as cardiac infarct, stroke, deafness, skin diseases, and cataracts. Therefore, inhibitors of connexin HCs have great pharmacological potential.

Suppression of wheat Fusarium head blight by novel amphiphilic aminoglycoside fungicide K20.

K20 is a novel amphiphilic aminoglycoside capable of inhibiting many fungal species. K20's capabilities to inhibit Fusarium graminearum the causal agent wheat Fusarium head blight (FHB) and to this disease were examined. K20 inhibited the growth of F.

One-step synthesis of carbohydrate esters as antibacterial and antifungal agents.

Carbohydrate esters are biodegradable, and the degraded adducts are naturally occurring carbohydrates and fatty acids which are environmentally friendly and non-toxic to human. A simple one-step regioselective acylation of mono-carbohydrates has been developed that leads to the synthesis of a wide range of carbohydrate esters. Screening of these acylated carbohydrates revealed that several compounds were active against a panel of bacteria and fungi, including Staphylococcus aureus, methicillin-resistant S.