Malaria, a life-threatening mosquito-borne disease caused by Plasmodium parasites, continues to pose a significant global health burden. Despite notable progress in combating the disease in recent years, malaria remains prevalent in many regions, particularly in Southeast Asia and most of sub-Saharan Africa, where it claims hundreds of thousands of lives annually. Flavonoids, such as the baicalein class of compounds, are known to have antimalarial properties. In this study, we rationally designed and synthesized a series of baicalein derivatives and identified a lead compound, FNDR-10132, that displayed potent in vitro antimalarial activity against Plasmodium falciparum (P. falciparum), both chloroquine-sensitive (60 nM) and chloroquine-resistant (177 nM) parasites. FNDR-10132 was evaluated for its antimalarial activity in vivo against the chloroquine-resistant strain Plasmodium yoelii N67 in Swiss mice. The oral administration of 100 mg/kg of FNDR-10132 showed 44% parasite suppression on day 4, with a mean survival time of 13.5 ± 2.3 days vs. 8.4 ± 2.3 days of control. Also, FNDR-10132 displayed equivalent activity against the resistant strains of P. falciparum in the 200–300 nM range. This study offers a novel series of antimalarial compounds that could be developed into potent drugs against chloroquine-resistant malarial parasites through further chemistry and DMPK optimization.

A sensitive and selective LC–MS/MS method was developed and validated for the simultaneous quantification of pretomanid and linezolid in BALB/c mouse plasma and lung tissue in accordance with ICH M10 bioanalytical guidelines. Chromatographic separation was achieved on a C18 column with gradient elution using methanol and 0.1% formic acid in water. The method demonstrated linearity ( r ² > 0.995), accuracy, precision, and recovery within the validated range of 10–20,000 ng mL ⁻¹ , without significant matrix effect. Stability under various storage and handling conditions was also confirmed. The validated assay was successfully applied to a pharmacokinetic study using a sparse sampling design, demonstrating reliable quantification of both analytes in plasma and lung tissue and confirming the applicability of the method to preclinical bioanalysis. The developed method provides a robust and validated analytical platform for the simultaneous determination of co-administered anti-tuberculosis agents and is suitable for future pharmacokinetic and tissue distribution studies in preclinical models.

Auranofin, an FDA‐approved oral anti‐rheumatic drug, was previously shown by our group to restrict Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) replication and pathology in preclinical models. Here, we systematically characterized its mechanism of action (MOA) through biochemical drug‐protein interactions, cell‐based mechanistic assays, and preclinical efficacy studies. Auranofin directly binds and inhibits SARS‐CoV‐2 MPro while simultaneously targeting multiple stages of the viral life cycle, disrupting endosomal trafficking, suppressing Spike S1/S2 proteolytic processing, impairing syncytia formation, and attenuating NF‐κB‐driven proinflammatory signaling. In cell culture, Auranofin demonstrated robust synergy with Remdesivir but competed with the MPro inhibitor Nirmatrelvir, informing rational combination design. In mice infected with the SARS‐CoV‐2 Delta variant, the oral combination of Auranofin and the Remdesivir prodrug GS‐621763 outperformed monotherapy, markedly reducing viral replication, inflammatory cytokine responses, and lung pathology, and improving clinical outcomes. These findings establish a multi‐target antiviral MOA of Auranofin and provide a mechanistic rationale for an all‐oral antiviral combination regimen against COVID‐19.

A novel and significant method was developed and validated with a sensitive, rapid, and simultaneous analytical method to determine antimicrobials in chicken tissues such as the kidney and liver. The process involved a unique approach to precipitation extraction. This method has not been widely used in this context, followed by the evaporation of the supernatant and reconstitution with the mobile phase. Antimicrobials, including Azithromycin, Clarithromycin, Erythromycin, Clavulanic acid, Ciprofloxacin, Clofazimine, Fluconazole, Linezolid, and Moxifloxacin were meticulously considered for development and validation in the chicken tissues. These antimicrobials were chosen based on their everyday use in poultry farming and their potential impact on human health. We used Ultra-Performance Liquid Chromatography with triple quad Mass Spectrometry and employed multiple reaction monitoring to detect the analytes of interest. All the compounds were well separated using Atlantis T3, 4.6x50mm, 3 μm. The linear range was set between 25 to 1000 ng/gm. The method was validated following linearity, extraction recovery, matrix effect impact, limit of detection, sensitivity, autosampler and benchtop stability, ensuring the results’ reliability and our method’s robustness.

According to a WHO report, antimicrobial resistance is one of the top 10 health threats. Environmental sources are extremely contaminated with high levels of antibiotics, antivirals and antifungals due to their excessive and unsafe usage. Hence, there is a need to detect and quantitate the antimicrobial agents in water. Consequently, a simultaneous analytical method is developed and validated, employing a solid-phase extraction methodology with an HLB cartridge. This method was utilized to quantify a minimum of twenty different chemicals derived from antibiotics, antivirals and antifungal drugs. Antibiotics include quinolones, isonicotinic acid, macrolides, oxazolidinones, penicillin, sulphonamides, antivirals that contain nucleotide class compounds and antifungals that comprising of triazoles and imidazoles. Ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC- S/MS) was used to quantify the analytes. Detection was achieved using multiple reaction monitoring with positive electron spray ionization. All the compounds were well separated with the column, Xterra MS C18 4.6 × 50 mm 2.5 μm, using water and acetonitrile with 0.1% formic acid as a mobile phase. The calibration curve range was set at 50 to 2000 ng mL-1. Validation parameters like precision and accuracy, matrix effect, sensitivity, autosampler stability, the limit of detection and recovery were performed.