Nitroimidazole Derivatives Research Articles

Machine learning approaches in designing anti-HIV nitroimidazoles: 2D/3D QSAR, kNN-MFA, docking, dynamics, PCA analysis and MMGBSA studies

In this study, newly synthesized 20 nitroimidazole derivatives were subjected to 2D and 3D Quantitative Structure-Activity Relationship (QSAR) study to investigate their anti-HIV activity against both ROD and IIIB strains. Later, proposed hypothesis was virtually proved by further in-silico studies. In statistically significant 2D-QSAR models r2 values for IIIB strains 0.9241 and for ROD strains 0.9412 with corresponding q2 values of 0.7706 and 0.8299, were obtained, respectively. Different models were constructed using three different kNN-MFA 3D QSAR approaches such as SW-FB, SA score, and GA. By using the generated hypothesis, newer analogues of nitroimidazole derivatives was designed and molecular modelling studies were conducted to prove the hypothesis. The three molecules were displayed the good docking scores compared to the reference molecule. The stabilities of docked complexes were analyzed by MD simulations and MMGB/SA calculations. These results offer insightful design guidance for novel anti-HIV compounds synthesis and suggest interesting directions for future pharmaceutical research.

IN VITRO EFFICACY OF VITEX AGNUS-CASTUS EXTRACTS AGAINST TRICHOMONAS VAGINALIS: A POTENTIAL THERAPEUTIC APPROACH

Aim and objectives: Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection globally. The current treatment, 5-nitroimidazole derivatives has raised concerns as a result of drug reliance, allergies, and drug resistance, driving efforts to identify alternative therapies. The Vitex species recognized for their pharmacological attributes including anti-inflammatory, antibacterial, antifungal, and antimicrobial properties are promising candidates for further investigation. Methods: In this study, the potential of Vitex agnus-castus extracts against T. vaginalis was explored. The water, ethanol, and 60% aqueous ethanol extracts from both leaves and fruits were examined for their effects on metronidazole (MET)-resistant (TV 50143) and sensitive strains (TV-78). Cytotoxicity was evaluated on L929 mouse fibroblast cells to determine the minimum lethal dose for each extract under aerobic and anaerobic conditions. Results: Antitrichomonial activity, cytotoxic activity and Selectivity Index (SI) values revealed distinct efficacy profiles. Leaf water extract displayed a balanced selectivity profile, while leaf 60% ethanol extract showed moderate to high selectivity. The fruit 60% ethanol extract exhibited significantly elevated selectivity with SI values of 2 and 1 under aerobic and anaerobic conditions, respectively, for the MET-sensitive reference strain, and 3 and 5, respectively, for the MET-resistant reference strain. Conclusion: These findings underscore the potential of the fruit 60% ethanol extract as a promising candidate for future drug development. Further investigations into its mechanisms and optimization are warranted to enhance its efficacy against T. vaginalis. Peer Review History: Received 13 May 2024; Reviewed 15 July 2024; Accepted 21 August; Available online 15 September 2024 Academic Editor: Dr. Amany Mohamed Alboghdadly, Ibn Sina National College for Medical Studies in Jeddah, Saudi Arabia, amanyalboghdadly@gmail.com Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Prof. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, alialkaf21@gmail.com Dr. Marwa A. A. Fayed, University of Sadat City, Egypt, maafayed@gmail.com Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my

Structural simplification of the 3‐nitroimidazo[1,2‐a]pyridine antileishmanial pharmacophore: Design, synthesis, and antileishmanial activity of novel 2,4-disubstituted 5-nitroimidazoles

Abstract As part of our ongoing antileishmanial structure–activity relationship study, a structural simplification of the 3‐nitroimidazo[1,2‐a]pyridine ring to a 5-nitroimidazole moiety was conducted. A series of novel 2,4-disubsituted 5-nitroimidazole derivatives, including the 5-nitroimidazole analog of Hit A and the 4-phenylsulfonylmethyl analog of fexinidazole, were obtained by using the vicarious nucleophilic substitution of hydrogen (VNS) reaction, to substitute position 4, and by using the tetrakis(dimethylamino)ethylene methodology to modulate position 2. The molecular structures of eight novel 5-nitroimidazoles were characterized by 1H NMR, 13C NMR, LC/MS, and HRMS. The in vitro antileishmanial activity of these compounds was evaluated against the promastigote form of Leishmania infantum and their influence on cell viability was assessed on the human hepatocyte HepG2 cell line. The 4-phenylsulfonylmethyl analog of fexinidazole showed the best selectivity index of the series, displaying good activity against both the promastigote form of L. infantum (EC50 = 0.8 µM, SI > 78.1) and the promastigote form of Leishmania donovani (EC50 = 4.6 µM, SI > 13.6), and exhibiting low cytotoxicity on the HepG2 cell line (CC50 > 62.5 µM).

Exploring new 5-Nitroimidazole Derivatives as Potent Acetylcholinesterase and Butyrylcholinesterase Enzyme Inhibitors.

Discovering new compounds capable of inhibiting physiologically and metabolically significant drug targets or enzymes is of paramount importance in biological chemistry. With this aim, new 5-nitroimidazole derivatives (1-4) were designed and synthesized, and their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were discovered using acetyl (butyryl) thiocholine and Ellman's reagents for spectrophotometric assay. The inhibitory profiles of the synthesized compounds were assessed by comparing their IC50 and Ki values. Results demonstrate significant inhibitory activity of all synthesized compounds against both AChE and BuChE compared to the reference compound, donepezil. Notably, compound 4 exhibited dual inhibition of these enzymes, showing the highest activity against Electrophorus electricus AChE (EeAChE) with a Ki value of 0.024±0.009 nM and against equine BuChE (eqBuChE) with a Ki value of 0.087±0.017 nM. Furthermore, molecular modeling was conducted to study the interaction modes of the most potent compound (4) and donepezil in the active site of their related enzymes' crystal structures (PDB ID: 4EY7 and 4BDS, respectively). Additionally, drug-likeness, ADME, and toxicity profiles of the compounds and metronidazole were predicted. The above results indicated that the dual inhibition of these enzymes is considered as a promising strategy for the treatment of neurological disorder especially Alzheimer's disease.

Antibiotic or gastric acid inhibitor use during pregnancy and postpartum depression: Population-based cohort study.

Postpartum depression is one of the most common non-obstetric postnatal complications. As the microbiome (and gut-brain axis) as well as inflammation may be involved in the mechanism, we aimed to assess if antibiotic or gastric acid inhibition use during pregnancy affects the risk of postpartum depression (clinical diagnosis and/or antidepressant use up to 1 year after childbirth). This population-based cohort study used first singleton pregnancy resulting in a live birth in Sweden from 2006 to 2016. Women with history of depression were excluded. Multivariable logistic regression models were used to assess the impact of antibiotics and gastric acid inhibitors and other risk factors, presented as odds ratios (ORs) with 95% confidence intervals (CI). Overall, 29% of all 10 666 women with postpartum depression were exposed to antibiotics and 6.2% to gastric acid inhibitors, compared to, respectively, 21% and 3.2% of 613 205 women without postpartum depression. Antibiotic use during pregnancy was associated with postpartum depression (OR 1.43, 95% CI 1.37-1.49), particularly for quinolones and other antibacterials (including nitroimidazole derivatives). Gastric acid inhibition was associated with an even higher risk than antibiotics (OR 2.04, 95% CI 1.88-2.21). Both antibiotics and gastric acid inhibitors suggested higher risk with increased dose in a dose-response analysis. The use of antibiotics and gastric acid inhibition drugs during pregnancy appeared to be associated with a higher risk of postpartum depression. However, it is important to consider that other predisposing factors could contribute to this increased risk, even after excluding individuals with a history of depression.

Evaluation of Ornidazole Tablets Bioequivalence in Chinese Healthy Participants Under Fasted and Fed Conditions Using Pharmacokinetic Parameters.

Ornidazole, the third generation of nitroimidazole derivatives after metronidazole and tinidazole, it exerts both bactericidal and antiprotozoal effects. The purpose of this study was to evaluate the pharmacokinetic and bioequivalence of two ornidazole tablets manufactured by two different manufacturers based on their pharmacokinetic parameters. Fasted and fed healthy Chinese volunteers participated in a randomized sequence, single-dose, open-label, two-period crossover trial. There were 24 participants in both the fed studyand the fastedstudy. Following a 7-day washout period before receiving the alternative formulation, eligible research participants were randomly assigned (1:1) to receive a single dosage of either the reference formulation or the test formulation. Following tablet administration, plasma samples were obtained over 72 h and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to evaluate ornidazole contents. maximum plasma concentration (Cmax), time to Cmax (Tmax),the area under the curve (AUC) from t = 0 to infinity (AUC0-∞), AUCfrom t = 0 to the last quantifiable concentration (AUC0-t), half-life (t1/2),and terminal elimination rate constant (z) were evaluated as pharmacokinetic (PK) parameters. The safety evaluation involved adverse events (AEs) incidence and alterations in laboratory tests (hepatic function, blood biochemistry, hematology, and urinalysis) or vital signs (temperature, pulse, and blood pressure). For the bioequivalence assessment in the fast trial, the prime PK parameters comparison between the reference and test formulation revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 100.97% (99.12-102.85%), 99.88% (90.63-110.08%), and 101.12% (99.17-103.11%), respectively. For the bioequivalence assessment in the fed trial, the key PK parameters comparison between the reference and test formulations revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 103.00% (100.94-105.11%), 101.90% (99.63-104.22%), and 102.99% (100.87-105.16%), respectively. The geometric mean ratios (GMRs) for the primary pharmacokinetic parameters (Cmax, AUC0-72, and AUC0-∞) between the two formulations and the corresponding 90% confidence intervals (CIs) were all within the range of 80.00-125.00% for both the fasting and fed states. Both treatments have comparable safety profiles. The bioequivalence and tolerability of ornidazole tablet reference and test formulations were evaluated among healthy Chinese participants under both fasting and fed conditions. The results indicated that both formulations were bioequivalent and generally well tolerated; besides, the interaction between food and drug may affect drug pharmacokinetics. CTR20212873, registered on 15 November 2021; ChiCTR2300069098, registered on 7 March 2023.

Synergistically Enhanced Electrochemical Sensing of Food Adulterant in Milk Sample at Erbium Vanadate/Graphitic Carbon Nitride Composite.

Dimetridazole (DMZ), a nitroimidazole derivative, is a notable antibiotic that has garnered growing interest in the medical community owing to its noteworthy pharmacological and toxicological properties. Increasing interest is being directed toward developing high-performance sensors for continuous monitoring of DMZ in food samples. This research investigated an electrochemical sensor-based nano-sized ErVO4 attached to a sheet-like g-CN-coated glassy carbon electrode to determine dimetridazole (DMZ). The chemical structure and morphological characterization of synthesized ErVO4@g-CN were analyzed with XRD, FTIR, TEM, and EDS. Irregular shapes of ErVO4 nanoparticles are approximately 15 nm. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were followed to examine the electrochemical performance in pH 7 phosphate buffer solution for higher performance. This electrochemical sensor showed a low detection limit (LOD) of 1 nM over a wide linear range of 0.5 to 863.5 µM. Also, selectivity, stability, repeatability, and reproducibility studies were investigated. Furthermore, this electrochemical sensor was applied to real-time milk sample analysis for the detection of analytes.

Using 5-Nitroimidazole Derivatives against Neglected Tropical Protozoan Diseases: Systematic Review

Neglected tropical diseases (NTDs) are a significant global health problem. Additionally, anti-protozoan treatments are toxic, and their therapeutic regimens require prolonged treatment times and high concentrations of the drugs. Additionally, multi-resistant protozoan strains represent an important global emergency that must be addressed. For these reasons, global efforts are being made to identify new drug candidates that are capable of combating these kinds of diseases. This systematic review shows that 5-nitroimidazole derivatives have been successfully used against neglected tropical protozoan diseases (NTPDs), with a specific focus on three diseases: malaria, leishmaniasis, and human trypanosomiasis. Some nitroimidazole derivatives have been repurposed, and an important group of new drugs is available for the treatment of NTPDs. Finally, we address 5-nitroimidazoles using chemoinformatics and medicinal chemistry tools to describe the most recent and promising 5-nitroimidazole derivatives associated with anti-protozoal activity using their published in vitro and in vivo data. We show that 5-nitroimidazoles offer a broader spectrum of activity against a variety of protozoal pathogens. More importantly, these compounds demonstrate a significantly reduced systemic toxicity compared to other nitroimidazoles. This makes them a more favorable option in the treatment of protozoal infections, particularly in scenarios where the patient’s tolerance to drug side effects is a critical concern.

Anti-toxoplasma activity and DNA-binding of copper(II) and zinc(II) coordination compounds with 5-nitroimidazole-based ligands.

Tetrahedral copper(II) and zinc(II) coordination compounds from 5-nitroimidazole derivatives, viz. 1-(2-chloroethyl)-2-methyl-5-nitroimidazole (cenz) and ornidazole 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (onz), were synthesized and spectroscopically characterized. Their molecular structures were determined by X-ray diffraction studies. The complexes [Cu(onz)2X2], [Zn(onz)2X2], [Cu(cenz)2X2] and [Zn(cenz)2X2] (X- = Cl, Br), are stable in solution and exhibit positive LogD7.4 values that are in the range for molecules capable of crossing the cell membrane via passive difussion. Their biological activity against Toxoplasma gondi was investigated, and IC50 and lethal dose (LD50) values were determined. The ornidazole copper(II) compounds showed very good antiparasitic activity in its tachyzoite morphology. The interaction of the coordination compounds with DNA was examined by circular dichroism, fluorescence (using intercalating ethidium bromide and minor groove binding Hoechst 33258) and UV-Vis spectroscopy. The copper(II) compounds interact with the minor groove of the biomolecule, whereas weaker electrostatic interactions take place with the zinc(II) compounds. The spectroscopic data achieved for the two series of complexes (namely with copper(II) and zinc(II) as metal center) agree with the respective DNA-damage features observed by gel electrophoresis.

Nitroimidazole derivatives potentiated against tumor hypoxia: Design, synthesis, antitumor activity, molecular docking study, and QSAR study.

A hypoxic environment occurs predominantly in tumors. During the growth phase of a tumor, it grows untilit exceedsits blood supply, leaving regions of the tumor in which the oxygen pressure is dramatically low. They are virtually absent in normal tissues, thus creating perfect conditions for selective bioreductive therapy of tumors. To this aim, a novel series of cytotoxic radiosensitizer agents were synthesized by linking the nitroimidazole scaffold with oxadiazole or triazole rings. The majority of the compounds exhibited moderate to excellent antiproliferative activitiestoward HCT116 cell line under normoxic and hypoxic conditions. The structure-activity relationship study revealed that compounds containing the free thiol group either in the oxadiazoles 11a,b or the triazoles 21a,b-23a,b demonstrated the strongest antiproliferative activity, which proves that the free thiol group plays a crucial role in the antiproliferative activity of our compounds under both normoxic (half-maximal inhibitory concentration[IC50 ] = 12.50-24.39 µM) and hypoxic conditions (IC50 = 4.69-11.56 µM). Radiosensitizing assay of the four most active cytotoxic compounds 11b and 21-23b assured the capability of the compounds to enhance the sensitivity of the tumor cells to the DNA damaging activity of γ-radiation (IC50 = 2.23-5.18 µM). To further investigate if the cytotoxicity of our most active compounds was due to a specific signaling pathway, the online software SwissTargetPrediction was exploited and a molecular docking study was done that proposed cyclin-dependent kinase2 (CDK2) enzyme to be the most promising target. The CDK2 inhibitory assay assured this assumption as five out of six compounds demonstrated a comparable inhibitory activitywith roscovitine, among which compound 21b showed threefold more potent inhibitory activity in comparison with the reference compound. A further biological evaluation proved compound 21b to have an apoptotic activity and cell cycle arrest activity at the G1 and S phases. During the AutoQSAR analysis, the model demonstrated excellent regression between the predicted and experimental activity with r2 = 0.86. Subsequently, we used the model to predict the activity of the test set compounds that came with r2 = 0.95.

Synthesis and Biological Evaluation of New Nitroimidazole Derivatives as Anti-Helicobacter pylori Agents Against Metronidazole-Resistant Strains

: Since several Helicobacter pylori strains have become resistant to metronidazole, new nitroimidazole derivatives based on metronidazole were designed and synthesized with different substituents on imidazole nitrogen. The activity of the synthesized compounds was evaluated against 20 clinically isolated metronidazole-resistant H. pylori strains. Some synthesized compounds were effective against those metronidazole-resistant H. pylori strains. Three compounds exhibited the most potent inhibitory activities (MIC50 = 8 µg/mL and MIC90 = 16 µg/mL).

Enhanced tumor specific drug release by hypoxia sensitive dual-prodrugs based on 2-nitroimidazole

Hypoxia in cancer is important in the development of cancer-selective medicines. Here, a novel hypoxia-responsible dual-prodrug is described. We designed and synthesized 2-nitroimidazole derivatives which spontaneously release both a PYG inhibitor and gemcitabine under hypoxic conditions. One such derivative, a prodrug 9 was found to be stable against chemical and enzymatic hydrolysis, and upon chemical reduction of the nitro group on imidazole, successfully releases both drugs. In an in vitro proliferation assay using human pancreatic cells, compound 9 exhibited significant anti-proliferative effects in hypoxia but fewer effects in normoxia. Consequently, prodrug 9 should be useful for cancer treatment due to its improved cancer selectivity and potential to overcome drug resistance.

Synthesis and Evaluation of 99mTc-Labelled 2-Nitroimidazole Derivatives with Different Linkers for Tumour Hypoxia Imaging.

When developing novel radiopharmaceuticals, a linker moiety between the chelator and targeting vector can have a crucial influence on adjusting the affinity of the tracer and its biodistribution in organisms. To develop novel 99mTc-labelled hypoxia imaging radiotracers, in this study, five isocyanide-containing 2-nitroimidazole derivatives with different linkers (L1, L2, L3, L4 and L5) were synthesised and radiolabelled with technetium-99m to obtain five stable 99mTc-complexes ([99mTc]Tc-L1, [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5). Corresponding rhenium analogues of [99mTc]Tc-L1 were synthesised and suggested the structures of these 99mTc-complexes would be a monovalent cation with a technetium (I) core surrounded by six ligands. [99mTc]Tc-L1 is hydrophilic, while the lipophilicities of [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5 are close. In vitro cell experiments showed that all five novel 99mTc-complexes had higher uptake in hypoxic cells compared with aerobic cells, which indicates the complexes have good hypoxia selectivity. The biodistribution of the five 99mTc-complexes in S180 tumour-bearing mice showed that they all had certain uptake in the tumours. Among them, [99mTc]Tc-L1 had the highest tumour-to-muscle (4.68 ± 0.44) and tumour-to-blood (3.81 ± 0.46) ratios. The introduction of polyethylene glycol (PEG) chains effectively reduced the lipophilicity and decreased uptake by the liver, intestine and blood but also increased clearance from the tumours. In vivo metabolic studies showed [99mTc]Tc-L1 kept intact and remained stable in tumour, blood and urine at 2 h post-injection. The results of SPECT imaging showed that [99mTc]Tc-L1 had significant tumour uptake at 2 h post-injection, but there was still high uptake in abdominal organs such as the liver and kidney, suggesting that this complex needs to be further optimised before being used for tumour hypoxia imaging.

Novel hybrid motifs of 4-nitroimidazole-piperazinyl tagged 1,2,3-triazoles: Synthesis, crystal structure, anticancer evaluations, and molecular docking study

4-((4-(1-benzyl-2-methyl-4-nitro-1H-imidazole-5-yl)piperazine-1-yl)methyl)-1-substituted-1H-1,2,3-triazole motifs are designed and synthesized via click chemistry. The reaction of 1-(N1-benzyl- 2-methyl-4-nitro-1H-imidazole- 5-yl)-4-(prop-2-yn-1-yl) piperazine 5 as new scaffold with diverse primary azides to selectively produce 1,4-disubstituted-1,2,3-triazoles 9a–k, 10a–c and 11a–q. Physicochemical methods: when 1H NMR, 13C NMR, and HRMS are utilized to fully characterize all synthesized compounds. X-ray structural determination and analysis for compound 9a is also performed. The newly designed chromophores are assessed for their anti-proliferative potency against three selected human cancer cell lines (MCF-7, HepG2, and PC3), and one normal cell line (Dermal/Fibroblast). Compounds 9g and 9k have shown potent activities against the MCF-7 cell line with IC50 values of (2.00 ± 0.03 μM) and (5.00 ± 0.01 μM) respectively. ADMET studies and Molecular docking investigations are performed on the most active hybrid nitroimidazole derivatives 9g and 9k with 4-hydroxytamoxifen (4-OHT) at the human estrogen receptor alpha (hER) during binding active sites to study the ligand–protein interactions and free binding energies at atomic levels. The triazole ring in the 9g derivative forms a hydrogen bond with Asp58 with distance 3.2 Å. And it is found that polar contact with His231 amino acid residue.In silico assessment of the compounds showed very good pharmacokinetic properties based on their physicochemical values, also the ADMET criteria of the most active hybrid systems are within the acceptable range.

18F]Fluoromisonidazole synthesis method: development and optimization by cartridge purification

Abstract [18F]Fluoromisonidazole ([18F]FMISO) as nitroimidazole derivative with 18F radioisotope is a widely known and studied hypoxia marker for PET imaging. A number of automated synthesis modules and purification strategies for production of [18F]FMISO have been described in recent years. The goal of this work was to develop [18F]FMISO synthesis process with Synthera module with solid phase extraction (SPE) Sep-Pak purification cartridges. To adjust the reaction conditions we synthesized [18F]FMISO under different reaction conditions and using various reversed-phase (RP) purification cartridges (HLB light, HLB plus, tC18, C18 environmental, Chromafix PS-RP). The synthesis was performed by nucleophilic substitution of commercial 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulfonylpropanediol precursor and subsequent acidic hydrolysis. Further, the product mixture was purified by passing through the SPE cartridge. The produced [18F]FMISO was retained on the cartridge, while the impurities passed through the cartridge into a waste. The retained [18F]FMISO was then eluted with small amounts of ethanol in water and eluates were collected in the final product vial. The product sample was subjected to quality control tests, while for waste sample chemical and radiochemical tests were performed. We have developed an efficient synthesis method of [18F]FMISO with cartridge purification with good radiochemical yield (RCY) and high chemical and radiochemical purity in accordance with the Ph. Eur. Monograph for Fluoromisonidazole (18F) injection.

Hydrothermal synthesis of cobalt germanium oxide supported with carbon-based graphitic carbon nitride for electrochemical determination of ornidazole

In recent decades, nitroimidazole derivatives have played an effectual role against bacterial and protozoan infections that can be used as anti-cancer and antibiotic drugs. Ornidazole (ORD) consists of a major 5-imidazole nucleus which complements to first nitro groups, ORD invades into lipid tissue and other nitroimidazole derivatives. The periodic intake of ORD orally causes side effects of headache, nausea, vomiting, and breathing difficulties such effects need potential monitoring and develop essential electrochemical sensing toward ORD. In this study, we developed a ternary cobalt germanium oxide (Co2GeO4) nanoparticle prepared by a facile hydrothermal method and followed by calcination. The carbon-based graphitic carbon nitride (GCN, g-C3N4) nanosheets were therefore supported for electrochemical sensing applications in order to improve the features like the catalytic activity, electrical conductivity, and active surface area of Co2GeO4 composites. The structural, chemical composition, and morphological properties of samples were characterized. Subsequently, the fabrication of cobalt germanium oxide with graphitic carbon nitride (Co2GeO4/GCN) was modified over a screen-printed carbon electrode (SPCE) towards electrochemical detection of ORD. Electrochemical measurements were recorded by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) for the determination of ORD. The Co2GeO4/GCN nanocomposite exhibits a wide linear range response of 0.049–94.9 μM in DPV with a nanomolar limit of detection of 7.2 nM of ORD and a high sensitivity of 2.66 µA µM−1 cm−2. An interference study was carried out for the Co2GeO4/GCN nanocomposite in the existence of hazardous metals, biological compounds, and similar drugs for examining the selectivity of the sensor. The proposed Co2GeO4/GCN nanocomposite reveals superior sensing selectivity towards ORD; hence, repeatability, reproducibility, and storage stability were recorded in their RSD and found to be less than 0.4%, adding to this practical feasibility of the sensor analyzed by real samples of blood serum & human urine with exceptional recovery percentages.

Synthesis and Structure Characterization of Three Pharmaceutical Compounds Based on Tinidazole

Tinidazole (TNZ), a 5-nitroimidazole derivative, has received increasing attention due to its pharmacological activities in treatment for amebic and parasitic infections. In this paper, we synthesized three novel drug supramolecular compounds successfully based on TNZ. The three compounds discussed were formed by TNZ and 2,6-dihydroxybenzoic acid (2,6-DHBA), 4-methylsalicylic acid (4-MAC), and 5-chloro-2-hydroxybenzoic acid (5-C-2-HBA). The N-H···O and O-H···O hydrogen bonds and weak C-H···O hydrogen bonds are the primary intermolecular forces in the construction of the three compounds. Crystal structure analysis revealed that all the compounds exhibit three-dimensional frameworks consisting of non-covalent interactions. Furthermore, six primary synthons, Ⅰ R22 (8), Ⅱ R21(6), Ⅲ R22(12), Ⅳ R33(9), Ⅴ R22(12), Ⅵ R33(9), formed through various hydrogen bonds are found in the three compounds. Moreover, the resulting pharmaceutical supramolecular compounds show improved stability. Single-crystal X-ray diffraction analysis, infrared spectroscopy (IR), element analysis, and thermogravimetric analysis (TGA) are reported.

Prospects for use of combined antibacterial drugs. Simprazol®: When whole is greater than sum

Today, in the pharmaceutical industry, many manufacturers produce so-called combined drugs containing 2 or 3 or more active ingredients. There are many reviews and studies in the world literature proving that most combinations, in contrast to sequential administration, often have a more pronounced synergistic effect of combined drugs. The use of such therapy increases patient compliance, while at the same time causing positive pharmacokinetic and other effects inherent in the combination, providing the clinician with new opportunities in the treatment of infections. Although the combination of fluoroquinolone and fixed-dose nitroimidazole derivatives is not as widely used in clinical practice, we present a review of Simprazole®, a combination of ciprofloxacin and ornidazole, analyzing the available data on clinical use and possible prospects that new drug.

N-[1-(2-Chlorophenyl)-2-{1-methyl-5-nitro-4-[(phenylsulfonyl)methyl]-1H-imidazol-2-yl}ethyl]-4-methylbenzenesulfonamide

In continuation of our research program to develop original synthetic methods using TDAE methodology on nitroheterocyclic substrates, we were able to generate for the first time a stable carbanion in position 2 of the 5-nitroimidazole scaffold. Starting from a 2-chloromethyl-4-phenylsulfonylmethyl-5-nitroimidazole intermediate, prepared by the vicarious nucleophilic substitution of hydrogen (VNS) reaction, we selectively introduced a N-tosylbenzylimine moiety at position 2 without reducing the sulfone at position 4, leading to the formation of N-[1-(2-chlorophenyl)-2-{1-methyl-5-nitro-4-[(phenylsulfonyl)methyl]-1H-imidazol-2-yl}ethyl]-4-methylbenzenesulfonamide in 47% yield. This new synthetic method using TDAE should allow access to new 2-substituted 5-nitroimidazole derivatives with various electrophiles such as carbonyls and other N-tosylbenzylimines.

Scandium-44: Diagnostic Feasibility in Tumor-Related Angiogenesis.

Angiogenesis-related cell-surface molecules, including integrins, aminopeptidase N, vascular endothelial growth factor, and gastrin-releasing peptide receptor (GRPR), play a crucial role in tumour formation. Radiolabelled imaging probes targeting angiogenic biomarkers serve as valuable vectors in tumour identification. Nowadays, there is a growing interest in novel radionuclides other than gallium-68 (68Ga) or copper-64 (64Cu) to establish selective radiotracers for the imaging of tumour-associated neo-angiogenesis. Given its ideal decay characteristics (Eβ+average: 632 KeV) and a half-life (T1/2 = 3.97 h) that is well matched to the pharmacokinetic profile of small molecules targeting angiogenesis, scandium-44 (44Sc) has gained meaningful attention as a promising radiometal for positron emission tomography (PET) imaging. More recently, intensive research has been centered around the investigation of 44Sc-labelled angiogenesis-directed radiopharmaceuticals. Previous studies dealt with the evaluation of 44Sc-appended avb3 integrin-affine Arg-Gly-Asp (RGD) tripeptides, GRPR-selective aminobenzoyl-bombesin analogue (AMBA), and hypoxia-associated nitroimidazole derivatives in the identification of various cancers using experimental tumour models. Given the tumour-related hypoxia- and angiogenesis-targeting capability of these PET probes, 44Sc seems to be a strong competitor of the currently used positron emitters in radiotracer development. In this review, we summarize the preliminary preclinical achievements with 44Sc-labelled angiogenesis-specific molecular probes.