Cocrystal structures formed by trithiocyanuric acid (TTCA) and selected nitroimidazole derivatives, dimetridazole (DMZ·TTCA, C5H7N3O2·C3H3N3S3), tinidazole (TNZ·TTCA·MeOH, C8H13N3O4S·C3H3N3S3·CH3OH), ornidazole (ONZ·TTCA·MeOH, C7H10ClN3O3·C3H3N3S3·CH3OH, and ONZ·TTCA·H2O, C7H10ClN3O3·C3H3N3S3·H2O) and ronidazole (RNZ·TTCA and 2RNZ·2TTCA, both C6H8N4O4·C3H3N3S3) were investigated to identify recurring drug-coformer aggregation patterns and factors determining supramolecular architecture. Structural analysis showed that TTCA adopts two principal supramolecular motifs: the hydrogen-bonded R2[2](8) dimer and linear chain assemblies. Two dominant drug-coformer binding schemes were identified. The first involves N-H...N hydrogen bonding in the para position relative to the TTCA dimer, leading to four-molecule assemblies, which are accompanied by heteronuclear hydrogen bonding in the ortho position. The second motif is associated with TTCA linear chains, where drug molecules are linked through N-H...N interactions and further stabilized by direct intermolecular or solvent-mediated hydrogen bonding. The polymorphic structure 2RNZ·2TTCA combines both supramolecular strategies within a single-crystal architecture. Hirshfeld surface analysis and intermolecular energy calculations confirmed the importance of hydrogen-bond competition in determining the crystal packing and supramolecular organization in TTCA-based cocrystals.

Trichomonas vaginalis is the pathogen responsible for trichomoniasis, a widespread sexually transmitted infection worldwide. Treatment currently relies solely on nitroimidazole-class drugs, such as metronidazole and tinidazole, to which resistance is increasingly reported. When resistance or treatment failure occurs, higher doses are prescribed, which in turn heightens the risk of toxic side effects. Therefore, discovering new therapeutic options is urgently needed. To address this, quantitative structure-activity relationship (QSAR) models were developed using nitroimidazole derivatives to analyze the relationship between various chemical structures and their efficacy against the parasite, selectivity between two different strains, and potential cytotoxicity against HeLa cells. Three distinct models were selected, demonstrating strong performance in both internal and external validation (external MCC values ranging from 0.583 to 0.849). These classification models were then applied to predict the biological activity of 57 nitroimidazole compounds, aiming to identify promising new candidates for treating T. vaginalis infections. Three selected hit compounds were synthesized and experimentally validated against T. vaginalis as well as HeLa cells. All compounds were active, with IC50 values ranging from 0.17 to 48.92 μM, with no cytotoxicity for HeLa cells observed at the tested concentrations, showing them to be promising candidates for preclinical evaluation.

A novel and highly sensitive electrochemical sensor based on an electropolymerized bromocresol green (BCG) film-modified pencil graphite electrode (poly(BCG)@PGE) was developed for the determination of tinidazole (TNDZ). The electropolymerization of BCG on the electrode surface significantly enhanced the electrochemical response toward TNDZ by improving electron-transfer kinetics and increasing the effective surface area. The fabrication and surface characteristics of the modified electrode were systematically investigated using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FT-IR). The electrochemical behavior of TNDZ was studied using CV and differential pulse voltammetry (DPV). Key experimental parameters affecting sensor performance, including the pH of the electrolyte solution, monomer concentration, and number of electropolymerization cycles, were optimized. Under the optimized conditions, the proposed sensor exhibited a wide linear dynamic range (LDR) from 0.4 to 500 µM for TNDZ determination, with a high sensitivity of 1402 µA·mM[-1]·cm[-2] and a low limit of detection (LOD) of 0.11 µM. The practical applicability of the developed voltammetric sensor was successfully demonstrated by the determination of TNDZ in artificial blood, pharmaceutical formulation, and spring water samples. The obtained results showed satisfactory recoveries with high precision and accuracy, confirming the reliability and potential applicability of the poly(BCG)@PGE sensor for sensitive electrochemical monitoring of TNDZ in complex matrices.

Metronidazole and tinidazole resistance with Trichomonas vaginalis is increasing. Paromomycin cream with high dose tinidazole is effective, though vulvovaginal ulceration has limited its use. We describe two patients who failed high dose tinidazole and boric acid who were successfully treated with tinidazole and paromomycin and summarize relevant literature. Summary: Paromomycin and tinidazole used in combination may be more effective than combination therapy with boric acid in eradicating treatment resistant trichomonas.

As part of efforts to identify genes associated with Trichomonas vaginalis resistance to 5-nitroimidazole drugs, thirty cryopreserved T. vaginalis isolates were revived and grown using Diamond's TYM medium. Minimum lethal concentrations (MLCs) for metronidazole (MTZ), tinidazole (TDZ), and secnidazole (SEC) were determined using a drug susceptibility assay. Transcriptome profiling was performed for 15 MTZ-sensitive (MTZ-S, MLC < 50 µg/mL) and 15 MTZ-resistant (MTZ-R, MLC ≥ 50 µg/mL) isolates using next-generation RNA sequencing. Bioinformatics analyses identified differentially expressed genes (DEGs). Among the MTZ-R isolates, six exhibited low MLCs of 50 µg/mL, five had intermediate MLCs between 100 and 200 µg/mL, and four had high MLCs ≥ 400 µg/mL. Differential gene expression analysis identified 28, 140, and 73 significantly altered genes in low-, intermediate-, and high-level MTZ resistance groups, respectively, with predominantly upregulated expression patterns. The SEC-resistant (SEC-R) isolates exhibited 136 differentially expressed genes, whereas the TDZ-resistant (TDZ-R) isolates showed minimal transcriptional changes. Focused analyses of iron transport pathways revealed reduced expression of ZIP-family iron import genes, particularly TvZIP4 (TVAG_273550), the strongest predictor of resistance in elastic-net modeling (AUC = 0.795). Resistant isolates also demonstrated coordinated upregulation of iron-sulfur cluster assembly and hydrogenosomal protein-import pathways. Weighted gene co-expression network analysis (WGCNA) identified multiple resistance-associated transcriptional modules correlated with MTZ and SEC MLCs. A comparative transcriptomic-proteomic analysis revealed concordant upregulation of iron-sulfur cluster machinery but discordant regulation of hydrogenosomal cargo proteins, likely supporting a post-transcriptional restriction model. These findings provide a broader mechanistic framework for understanding 5-nitroimidazole resistance in T. vaginalis and identifying candidate biomarkers and pathways that may support future therapeutic and diagnostic development.

Banana peel (BP) has gained attention as a sustainable, low-cost biosorbent for removing pharmaceuticals from aquatic environments. In this study, BP was modified using a choline chloride/methanesulfonic acid (ChCl/MSA) deep eutectic solvent to produce a chemically and structurally enhanced material (BP-ChCl/MSA) for pharmaceutical adsorption from water. The modified biosorbent was comprehensively characterized by FTIR, TGA, and SEM analyses, and its performance was systematically compared with BP treated solely with methanesulfonic acid (BP-MSA). MSA induced holocellulose hydrolysis and ChCl/MSA increased the lignin content in the biosorbent. Propranolol (PRO), metformin, and tinidazole were used as model drugs. BP-ChCl/MSA showed selective adsorption for PRO, with almost 90% of removal efficiency achieved from an initial concentration of 20.0 mg L-1, without requiring pH adjustment at 25 °C. The PRO adsorption kinetics for both BP-MSA and BP-ChCl/MSA were best described by the pseudo-second-order (PSO) model, with adsorption occurring in less than 500 min. Isotherms were well described by the Sips model, indicating adsorption on a heterogeneous surface, with BP-ChCl/MSA exhibiting higher maximum adsorption capacity value (284.6 mg g-1) than BP-MSA (238.1 mg g-1). Thermodynamic analysis using the partition model provided more consistent results, with Δads G ◦ ranging from -24.1 to -21.9 kJ mol-1 as the temperature increased from 25 to 40 °C, showing an endothermic process (ΔadsH◦ = 23.5 kJ mol-1) that is entropy-driven (ΔadsS◦ around 0.15 kJ mol-1 K-1). Overall, ChCl/MSA treatment enhanced the interactions between the remaining lignin functional groups and PRO, mainly through electrostatic interactions and hydrogen bonding. Moreover, the material showed good reusability, maintaining more than 75% of removal efficiency after 3 adsorption cycles. These results demonstrate that treatment with the ChCl/MSA DES significantly improved the adsorption capacity of BP through an efficient and eco-friendly approach, yielding a sustainable and promising material for drug adsorption in aqueous media.

Now, numerous synthetic medications are available for managing giardiasis, such as metronidazole, furazolidone, and tinidazole. These pharmaceuticals are associated with various adverse effects. The present experimental investigation aims to assess the in vitro and in vivo effects of silver nanoparticles (SNP) synthesized Astragalus baba-alliar extract against Giardia lamblia. The precipitation technique was utilized for the eco-friendly synthesis of SNP by reducing silver ions. An in vitro study was conducted on G. lamblia cysts and trophozoites following exposure to varying concentrations of SNP (10-200 µg/mL) for durations ranging from 10 to 360 min. The impact of SNP on trophozoite plasma membrane integrity and its cytotoxic effects on both normal and colon cancer cells were evaluated. In the subsequent in vivo experiment, BALB/c mice infected with Giardia were administered SNP at doses of 10, 15, and 20 mg/kg/day for a duration of one week. Stool examinations were conducted on the 8th day post-infection to assess the presence of Giardia cysts and determine the reduction rate. The study found that the size of synthesized SNP ranged from 10 to 90 nm, with the highest concentration of particles falling within the 35-45 nm range. The administration of SNP significantly elevated the mortality rate of G. lamblia cysts in a dose-dependent manner. Specifically, at concentrations of 100 and 200 μg/mL, SNP effectively eradicated G. lamblia cysts after 120 and 240 h, respectively. In an in vivo setting, the treatment of infected mice with SNP at doses of 10, 15, and 20 mg/kg likewise led to a dose-dependent reduction in the viability of G. lamblia cysts. Exposing G. lamblia trophozoites to SNP led to a dose-dependent elevation in the permeability of trophozoite plasma membranes. The 50% cytotoxic concentrations (CC50) values of SNP for colon cancer and normal cell lines were measured at 361.7 μg/mL and 769.9 μg/mL, respectively. The calculated selectivity index value, which exceeds 2 (2.13), suggests that the SNP demonstrates a higher safety profile for normal cells compared to cancer cells. The experimental investigation demonstrated that SNP produced using A. baba-alliar exhibited significant anti-Giardia activity both in laboratory settings (in vitro) and in living organisms (in vivo), suggesting its potential as a treatment for Giardia infections. However, further studies are needed to elucidate the precise mechanisms of action and thoroughly evaluate the toxicity profile of this type of SNP.

This study integrates computational fluid dynamics (CFD) simulations with machine learning (ML) models to develop a framework for predicting drug release from hydroxypropyl methylcellulose (HPMC) matrices. Transient, three-dimensional CFD models were constructed to solve the conservation equations for fluid flow and mass transfer, explicitly simulating the swelling front propagation, polymer dissolution, and diffusive drug release from a cylindrical HPMC carrier into a dissolution medium. The key results from parametric CFD studies quantified the nonlinear relationship between initial drug loading and the resultant concentration gradients and release rates over time, providing a high-resolution dataset on the underlying transport phenomena. These CFD simulations were validated against experimental release data, achieving excellent agreement (mean absolute error of 1.54% and R-squared of 0.9997). The CFD-generated data, combined with experimental measurements from the literature for eight model drugs (ribavirin, ranitidine hydrochloride, isoniazid, diltiazem hydrochloride, theophylline, tinidazole, sulfamethoxazole, and propylthiouracil), were used to train the machine learning techniques. A systematic topology search identified an optimized least-squares support vector regression (LS-SVR) as the most accurate predictor. This LS-SVR model, configured with the Gaussian kernel function, successfully predicts the overall dataset with an R-squared of 0.99850, an average absolute relative deviation of 1.27%, and a root mean squared error of 0.833. This hybrid CFD-ML approach provides a powerful tool for the rational design of HPMC-based drug formulations with targeted release profiles.

We present two clinical cases of intestinal amoebiasis. The first case was asymptomatic, with colonic ulcers incidentally detected during colonoscopy. The second case presented with diarrhea and a hepatic abscess, also associated with colonic ulcers. Both patients showed a favorable clinical outcome following treatment. Amoebiasis is caused by the parasite Entamoeba histolytica. It is transmitted via the fecal-oral route and is more common among travelers, immunocompromised individuals, and men who have sex with men. Clinically, it can range from asymptomatic infection to severe colitis and hepatic abscess formation. Diagnosis is established through stool microbiological tests, serology, and intestinal biopsies. In invasive cases, treatment consists of metronidazole or tinidazole, followed by a luminal amoebicide such as paromomycin. In cases of large abscesses, drainage may be required.

Trichomonas vaginalis is the causative agent of trichomoniasis, the most common and prevalent sexually transmitted infection (STI) globally, with about 156 million cases annually. Trichomoniasis is a critical public health problem, and it is aggravated due to its association with a higher risk of HIV-1 acquisition and transmission and complications such as preterm delivery and pelvic inflammatory disease. This STI is treated mainly through the 5-nitroimidazole class, specifically metronidazole and tinidazole. However, drug resistance, which can represent between 5 and 20% of clinical cases, and hypersensitivity reactions are a general concern. In this context, drug development for trichomoniasis is an ever-growing research field. Therefore, considering how important drug targets and the mechanism of action of compounds can be to drug discovery, there is a growing interest in better understanding how some molecules can be used as targets. This article offers an overview of T. vaginalis drug targets, their significance in metabolism, pathogenesis, or survival, and their contribution to drug development for trichomoniasis.