Antiproliferative Aspect of Benzimidazole Derivatives’ Activity and Their Impact on NF-κB Expression

Benzimidazoles belong to a new class of bioreductive agents with cytotoxic activity towards solid tumor cells, especially in their first stage of growth, which is characterized by low oxygen concentration. Bioreductive agents represent a class of prodrugs that target hypoxic tumor cells. Their bioactivity depends on the reactivity of their functional chemical groups. Their efficacy requires metabolic reduction and subsequent generation of toxic prodrugs. Chemoresistance of tumor cells is a major problem for successful antitumor therapy for many types of tumors, especially for breast cancer. The present study was performed to assess the effect of the antiproliferation activity of the tested benzimidazoles by way of NF-κB expression inhibition. The activity of the tested compounds on T47D and MCF7 cells was examined by WST, western blot, NF-κB transactivation assay, and apoptotic cell population analysis. Compound 3 was highly cytotoxically active against T47D cells, especially in hypoxic conditions. Its IC50 of 0.31 ± 0.06 nM, although weaker than tirapazamine, was significantly higher than the other tested compounds (2.4–3.0 fold). The increased bax protein expression upon exposure to the tested compounds indicated intercellular apoptotic pathway activity, with tumor cell death by way of apoptosis. Increased bax protein synthesis and apoptotic cell dominance upon treatment, especially with N-oxide derivatives (92% apoptotic cells among T47D cell populations during treatment with compound 3), were correlated with each other. Additionally, both increased bax protein and decreased NF-κB protein expression supported antiproliferative activity via NF-κB–DNA binding inhibition associated with the tested compounds. Compound 3 appeared to be the strongest inhibitor of NF-κB expression in hypoxic conditions (the potency against NF-κB expression was about 75% of that of tirapazamine). The present studies involving this class of heterocyclic small molecules proved their potential usefulness in anticancer therapy as compounds be able to limit tumor cell proliferation and reverse drug resistance by NF-κB repression.

Biosynthesis of Ultrasonically Modified Ag-MgO Nanocomposite and Its Potential for Antimicrobial Activity

This study reports a green synthesis route for a bilayered Ag-MgO nanocomposite using aqueous peel extract of Citrus paradisi (grapefruit red) under an accelerated uniform heating technique and its antibacterial potency against Escherichia coli. Surface modifications and composition of the nanocomposite were examined using a UV-visible spectrophotometer, transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM) equipped with an energy dispersive X-ray (EDX) analyzer. The efficiencies of the as-synthesized Ag-MgO nanocomposite against Escherichia coli were examined. The synthesized Ag-MgO nanocomposite showed characteristic synergetic bands at 290 nm for MgO nanoparticle and at around 440 nm for Ag nanoparticle which blue-shifted to 380 nm in the composite. A spherically dispersed nanocomposite with cubical crystal lattice network with a diameter of about 20–100 nm comprising Ag nanoparticle embedded within MgO nanoparticles was obtained. The nanocomposite produced stronger antibacterial activity against Escherichia coli as compared to MgO nanoparticle, indicating a higher interaction between Ag and MgO ions. The nanocomposite was successfully synthesized via an efficient modified method by bioreductive agents with an improved synergistic antibacterial property towards water purification.

Nitroimidazoles with a halogen-containing side-chain

Syntheses are reported for: nine 2-nitroimidazoles, the abbreviated names all beginning with E, based on derivation from Etanidazole); five 2-methyl-5-nitroimidazoles (M compounds, derived from Metronidazole); and five 2-methyl-4-nitroimidazoles (labelled 2M4N compounds). The nitroimidazoles all have an amide side-chain at the N1 atom of the imidazole, with 17 of them containing one to five halogen atoms. The aim is to study compounds for comparison with EF5 (the number showing the presence of five F-atoms), a previously reported, pentafluoropropylacetamide derivative of 2-nitroimidazole that is currently used as a hypoxia marker drug to detect cancerous tumours. The new compounds are characterized by standard methods, including X-ray structural data for the fluorinated MF5, 2M4NF5, and 2M4NF1(−1) species, with the “–1” indicating two C-atoms in an alkylamide chain rather than the three C-atoms in the propylacetamide of EF5. Intra- and inter-molecular H-bonding is seen in the solid state structures, likely an important property in biological use; another key property of the nitroimidazoles is their reduction potentials, and the measured CV data confirm that 2NO2Im compounds with longer side-chains and more F-atoms (like EF5) are worth investigating for possible activity as hypoxia-selective, bioreductive agents.