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This review delves into recent advancements in the field of nitro(het)aromatic bioreductive agents tailored for hypoxic environments. These compounds are designed to exploit the low-oxygen conditions typically found in solid tumors, making them promising candidates for targeted cancer therapies. Initially, this review focused on their role as gene-directed enzyme prodrugs, which are inert until activated by specific enzymes within tumor cells. Upon activation, these prodrugs undergo chemical transformations that convert them into potent cytotoxic agents, selectively targeting cancerous tissue while sparing healthy cells. Additionally, this review discusses recent developments in prodrug conjugates containing nitro(het)aromatic moieties, designed to activate under low-oxygen conditions within tumors. This approach enhances their efficacy and specificity in cancer treatment. Furthermore, this review covers innovative research on using nitro(het)aromatic compounds as fluorescent probes for imaging hypoxic tumors. These probes enable non-invasive visualization of low-oxygen regions within tumors, providing valuable insights for the diagnosis, treatment planning, and monitoring of therapeutic responses. We hope this review will inspire researchers to design and synthesize improved compounds for selective cancer treatment and early diagnostics. [ABSTRACT FROM AUTHOR]

(1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing colchicine-like and catechol-like moieties with methyl group substitution in the benzimidazole ring against highly invasive breast cancer cell line MDA-MB-231 and their related impairment of tubulin dynamics. (2) Methods: The antiproliferative activity was assessed with the MTT assay. Alterations in tubulin polymerization were evaluated with an in vitro tubulin polymerization assay and a docking analysis. (3) Results: All derivatives showed time-dependent cytotoxicity with IC50 varying from 40 to 60 μM after 48 h and between 13 and 20 μM after 72 h. Immunofluorescent and DAPI staining revealed the pro-apoptotic potential of benzimidazole derivatives and their effect on tubulin dynamics in living cells. Compound 5d prevented tubulin aggregation and blocked mitosis, highlighting the importance of the methyl group and the colchicine-like fragment. (4) Conclusions: The benzimidazole derivatives demonstrated moderate cytotoxicity towards MDA-MB-231 by retarding the initial phase of tubulin polymerization. The derivative 5d containing a colchicine-like moiety and methyl group substitution in the benzimidazole ring showed potential as an antiproliferative agent and microtubule destabilizer by facilitating faster microtubule aggregation and disrupting cellular and nuclear integrity. [ABSTRACT FROM AUTHOR]

In the present work we studied the interactions of a newly synthesized drug candidate, 2-(2-hydroxy-4-methoxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine (2H4MBBH), with human serum albumin (HSA) by fluorescence spectroscopy. 2H4MBBH-HSA binding parameters were assessed by fluorescence quenching strategy. As made clear by the concentration data, 2H4MBBH unequivocally quenched the instrinsic HSA fluorescence. The calculated Stern-Volmer quenching constant Ksv, the Ka of 2H4MBBH-HSA complexes, as well as the thermodynamic parameters ∆H°, ∆S° and ∆G°, showed that the H-bonding forces play major part in the interaction of 2H4MBBH with HSA. These calculations point to a quenching component based on 2H4MBBH-HSA static complex formation rather than energetic collisions. [ABSTRACT FROM AUTHOR]

Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of their anti-proliferative properties is of great pharmacological interest. Some 2-alkyl-4-amino-thieno[2,3-d]pyrimidines 2–5 were synthesized, and their cyto- and phototoxicity against BALB 3T3 cells were established by an in vitro 3T3 NRU test. The obtained results indicate that the tested compounds are not cytotoxic or phototoxic, and that they are appropriate to be studied for their anti-proliferative and anti-tumor properties. The anti-proliferative potential of the compounds was investigated on MCF-7 and MDA-MB-231 cancer cells, as well as a MCF-10A cell line (normal human mammary epithelial cells). The most toxic to MCF-7 was thienopyrimidine 3 with IC50 13.42 μg/mL (IC50 0.045 μM), followed by compound 4 (IC50 28.89 μg/mL or IC50 0.11 μM). The thienopyrimidine 4 revealed higher selectivity to MCF-7 and lower activity (IC50 367 μg/mL i.e., 1.4 μM) than compound 3 with MCF-10A cells. With respect to MDA-MB-231 cells, ester 2 manifested the highest effect with IC50 52.56 μg/mL (IC50 0.16 μM), and 2-ethyl derivative 4 revealed IC50 62.86 μg/mL (IC50 0.24 μM). It was estimated that the effect of the substances on the cell cycle progression was due to cell cycle arrest in the G2 stage for MDA-MB-231, while arrest in G1 was detected for the estrogen (ER)-positive MCF-7 cell line. The tested compound's effects on the change of the zeta potential in the tumorigenic cells utilized in this study were determined. The calculation which we performed of the physicochemical properties and pharmacokinetic parameters influencing the biological activity suggested high intestinal absorption, as well as drug-likeness. [ABSTRACT FROM AUTHOR]

1H-benzimidazol-2-yl hydrazones with varying hydroxy and methoxy phenyl moieties were designed. Their effect on tubulin polymerization was evaluated in vitro on porcine tubulin. The compounds elongated the nucleation phase and slowed down the tubulin polymerization comparably to nocodazole. The possible binding modes of the hydrazones with tubulin were explored by molecular docking at the colchicine binding site. The anticancer activity was evaluated against human malignant cell lines MCF-7 and AR-230, as well as against normal fibroblast cells 3T3 and CCL-1. The compounds demonstrated a marked antineoplastic activity in low micromolar concentrations in both screened in vitro tumor models. The most active were the trimethoxy substituted derivative 1i and the positional isomers 1j and 1k, containing hydroxy and methoxy substituents: they showed IC50 similar to the reference podophyllotoxin in both tumor cell lines, accompanied with high selectivity towards the malignantly transformed cells. The compounds exerted moderate to high ability to scavenge peroxyl radicals and certain derivatives—1l containing metha-hydroxy and para-methoxy group, and 1b-e with di/trihydroxy phenyl moiety, revealed HORAC values high or comparable to those of well-known phenolic antioxidants. Thus the 1H-benisimidazol-2-yl hydrazones with hydroxy/methoxy phenyl fragments were recognized as new agents exhibiting promising combined antioxidant and antineoplastic action. [ABSTRACT FROM AUTHOR]

Four sets of samples of anodically prepared ZnO thin films were tested as potential photocatalysts for degradation of methyl orange (MO). The results show that the best properties belong to the samples prepared by anodization in oxalic acid and subsequently annealed 3 hours at 341°C. The dependences of the rate of the reaction on the time of use of the photocatalyst, the temperature of the decomposition reaction, the pH of the solution and the illumination were investigated too. The activation energies of the reactions were derived from the dependence of the rate of the reaction on the temperature. The properties of the acquired ZnO anodic films, as well as their compositions and structures were investigated by various analytical techniques, as follows: Attenuated Total Reflection Fourier Transformation Infrared Spectroscopy (ATR-FTIR), X-ray Diffractometry (XRD), Atomic Force Microscopy (AFM), Inductively Coupled Plasma - Optical Emission Spectroscopy (ICP-OES), Scanning Electron Microscopy (SEM) and UV-VIS Spectrophotometry. [ABSTRACT FROM AUTHOR]

In the present study series of triazole-, thiadiazole- and thiosemicarbazone-benzimidazole hybrid compounds were synthesized as potential anti-cancer agents. In order to determine their antitumor potential and cytotoxic effect (via MTT assay) lung adenocarcinoma (A549) and breast cancer (MDA-MB-231) cell lines were examined. For detection of apoptosis induced by drug treatment, DAPI staining was performed in order to observe the apoptotic alterations in cell nuclei. It was found that the thiadiazole derivative 12 leads to the occurrence of micronuclei, suggesting genotoxic effect. Furthermore, a wound healing assay was performed in order to test whether any changes in cell motility occurred upon treatment with the newly synthesized hybrids, since both cell lines are examples of highly invasive tumours. The cell motility of MDA-MB-231 was impeded mostly by compound 12 (15 % of wound closure) and in A549 compound 9 reduced cell motility by 46 % compared to the control. The obtained results suggest that compound 12 possesses a promising anticancer effect. [ABSTRACT FROM AUTHOR]

New 1,3-disubsituted benzimidazol-2-ones are synthesized in order to evaluate their anti-trichinellosis efficacy. Solid-liquid phase transfer catalysis as the most readily available synthesis method was used to prepare the target compounds. The precursors required for the synthesis of the disubstituted benzimidazoles were obtained by means of two methods. Structures analysis of the compounds by means of IR, 1H NMR analysis was performed. The molecular geometry and electron structure of these molecules were evaluated using density functional theory (DFT) methods. Antitricinellosis activity of the compounds was investigated. The parasitological study in vitro showed that some of the tested benzimidazolones possessed higher activity against Trichinella spiralis than albendazole. The data of SAR for most of the tested compounds are comparable with those of albendazole. [ABSTRACT FROM AUTHOR]

This is the first report on the synthesis of vitamin B9-Rapana thomasiana hemocyanin conjugates (vit. B9-RtH). Proteins modified with 25 and 150 vitamin B9 residues аre obtained in a coupling reaction between N-hydroxysuccinimide-activated γ -carboxylic groups of vitamin B9 and the amino-groups of N-terminal amino acids and lysines comprising the protein. ATR-FTIR spectroscopy is applied to monitor the changes of the secondary structure upon the modification. The comparison of the secondary structure of the native and the vitamin B9-conjugated RtHs shows that the modification results in an increase of the β-structures in a favor of α-helices and coiled structures. The therrmal stability of the novel preparations is evaluated by differential scanning calorimetry (DSC). Despite the serious changes of the conformation, the vit.-B9-RtH conjugates are characterized by a high thermal stability. It is assumed that the changes of the DSC profiles are due to alternative protein-protein interactions, e.g H-bonding, stacking or hydrophobic interactions with vitamin B9 moieties that are possible in the modified RtH molecules. [ABSTRACT FROM AUTHOR]

Copyright of Acta Medica Medianae is the property of Acta Medica Medianae and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Medica Medianae is the property of Acta Medica Medianae and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The development of ionic liquids based on active pharmaceutical ingredients (API-ILs) is a possible solution to some of the problems of solid and/or hydrophobic drugs such as low solubility and bioavailability, polymorphism and an alternative route of administration could be suggested as compared to the classical drug. Here, we report for the first time the synthesis and detailed characterization of a series of ILs containing a cation amino acid esters and anion ketoprofen (KETO-ILs). The affinity and the binding mode of the KETO-ILs to bovine serum albumin (BSA) were assessed using fluorescence spectroscopy. All compounds bind in a distance not longer than 6.14 nm to the BSA fluorophores. The estimated binding constants (KA) are in order of 105 L mol−1, which is indicative of strong drug or IL-BSA interactions. With respect to the ketoprofen-BSA system, a stronger affinity of the ILs containing l-LeuOEt, l-ValOBu, and l-ValOEt cation towards BSA is clearly seen. Fourier transformed infrared spectroscopy experiments have shown that all studied compounds induced a rearrangement of the protein molecule upon binding, which is consistent with the suggested static mechanism of BSA fluorescence quenching and formation of complexes between BSA and the drugs. All tested compounds were safe for macrophages. [ABSTRACT FROM AUTHOR]

The title compound, C16H9NO4, also known as the 3-benzoylpyridinium betaine of squaric acid, exhibits a dipolar electronic ground-state structure with a positively charged pyridinium fragment and a negatively charged squarate moiety. In the molecule, the two aromatic rings are twisted by 56.03 (2)° relative to one another. The three-dimensional packing of the molecules is stabilized by C—H··O· short contacts. [ABSTRACT FROM AUTHOR]

A study which evaluated the possibility of applying spectroscopic techniques such as nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy in the characterization of extracts from the pericarp, placenta, seeds and stalk of red hot pepper is presented.

The article discusses a study which examined the chemical structure of nitrofurantoin radical anion via infrared spectroscopy and density functional theory.

In vitro antioxidant activity of two cyclodidepsipeptides, 3-(2-methylpropyl)-6-(propan-2-yl)-4-methyl-morpholine-2,5-dione and 3,6-di(propan-2-yl)-4-methyl-morpholine-2,5-dione, was investigated. Our data indicate moderate antioxidant potentials of the two studied cyclodepsipeptides. A high correlation between 2,2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging capacity and total reducing power were found. According to the density functional theory (DFT) calculations, the most probable mechanism of antioxidant action is hydrogen atom abstraction from the activated C-H group at 3-position in the morpholinedione ring. To the best of our knowledge this is the first report about the antioxidant properties of morpholine-2,5-diones derivatives. [ABSTRACT FROM AUTHOR]

Parasitic infections, caused mainly by the species Trichinella spiralis ( T. spiralis ), are widespread around the world and lead to morbidity and mortality in the population. Meanwhile, some studies have showed that these parasites induce oxidative stress in the infected host. With the aim of developing a class of compounds combining anthelmintic with antioxidant properties, a series of new benzimidazolyl-2-hydrazones 5a-l, bearing hydroxyl- and methoxy-groups, were synthesized. The anthelmintic activity on encapsulated T. spiralis was studied in vitro thus indicating that all hydrazones were more active than the clinically used anthelmintic drugs albendazole and ivermectin. 5b and 5d killed the total parasitic larvae (100% effectiveness) after 24 hours incubation period at 37 °C in both concentrations (50 and 100 μg ml -1 ). The antioxidant activity of the target compounds was elucidated in vitro against stable free radicals DPPH and ABTS as well as iron induced oxidative damage in model systems containing biologically relevant molecules lecithin and deoxyribose. The two 2,3- and 3,4-dihydroxy hydrazones 5b and 5d were the most effective radical scavengers in all studied systems. DFT calculations were applied to calculate the reaction enthalpies in polar and nonpolar medium and estimate the preferred mechanism of antioxidant activity. The relative radical scavenging ability of compounds 5a-l showed a good correlation to the experimentally observed trends. It was found that the studied compounds are capable to react with various free radicals - ˙OCH 3 , ˙OOH and ˙OOCH 3 , through several possible reaction pathways - HAT in nonpolar medium, SPLET in polar medium and RAF in both media., Competing Interests: The authors declare that there is no conflict of interests related to this study., (This journal is © The Royal Society of Chemistry.)