Benzimidazole derivatives as a new scaffold of anticancer agents: Synthesis, optical properties, crystal structure and DFT calculations.

The absolute necessity to fight some class of tumour is perceived as serious health concerns, and the discovery and development of effective anticancer agents are urgently needed. So, the novel benzimidazole derivatives (2a-b) were designed, synthesized, with their structures rigorously characterized using single X-ray crystallography, FT-IR, UV, and NMR spectroscopy, alongside elemental analysis. The geometric structures were optimized using density functional theory (DFT) calculations performed at the ωB97X-D/cc-pVDZ level, yielding good agreement with experimental XRD data. The studied salt complexes exhibited the ability to absorb UV light at 275 nm. Furthermore, anticancer activity of the compounds was screened against (MDA-MB-231, MCF-7, HT-29 and healthy cell line (HF)) and revealed the remarkable efficacy of select newly synthesized Benzimidazole derivatives (2a-b). Compound 2a showed relative significant higher cytotoxicity (165.02) in MDA-MB-231 cancer cell line. This underscores their promising potential in therapeutic applications, affirming their role as valuable contenders in the pursuit of novel anticancer agents.

Water-soluble silver(i) complexes with N-donor benzimidazole ligands containing an imidazolium core: stability and preliminary biological studies.

Herein, we report the synthesis, characterisation and preliminary biological evaluation of two novel silver(i) complexes of type [AgL2](NO3)3 (3 and 4) with ionic N-donor benzimidazoles. The complexes have been synthesized by the reaction of 1.5 equivalents of silver nitrate and N-donor benzimidazoles containing an imidazolium core at the 2-position (1 and 2) in ethanol. The X-ray analysis of 4 shows that it has two free imidazolium cores and the charge is balanced with three nitrate anions. A study by the combination of NMR, IR, LC-MS and elemental analysis techniques also suggests that the complexes have this structure both in the solid-state and solution. The complexes are highly soluble and stable in water. Cytotoxicity evaluation against four cancerous human cells and one non-cancerous human cell revealed that the complexes have no significant anti-growth effect. However, the complexes showed a remarkable antimicrobial effect at normalized minimum inhibitory concentrations (normalized MICs) in the range of 33-268 µM against a panel of microorganisms consisting of Gram-negative and Gram-positive bacteria, and fungi.

Synthesis, structural, cytotoxic and pharmacokinetic evaluation of some thiosemicarbazone derivatives.

Iron(III) and nickel(II) complexes bearing a thiosemicarbazone framework were synthesized by a one-pot synthesis method. The structures were characterized by elemental analysis, IR, 1 H NMR, APCI Mass, conductivity, magnetic moment measurements. Molecular and crystal structures of the iron(III) complex were obtained from single-crystal X-ray diffraction. The findings showed that the metal atom adopts a slightly distorted square-pyramidal coordination, with the four donor atoms of the thiosemicarbazone ligand defining the basal plane and a chloride atom occupying the apical position. In the crystal lattice, the structure is stabilized by intermolecular O─H···O and C─H···O interactions. The cytotoxic activity was studied by MTT assay, the expression levels of cytochrome P450 (CYP) enzymes by Western blot, and the lipophilicity (LogP) by using the shake-flask method, another pharmacokinetic parameter. The findings showed that the IC50 values decreased with the decrease of the LogP values of the substances. Cytochrome P450 expression levels were found specific for each compound and each cell line. As a result, the pharmacokinetic properties of the newly synthesized thiosemicarbazone compounds are crucial for oral administration and provide us with clues for prospective in vivo studies.

Investigations of antiproliferative and antioxidant activity of ß-lactam morpholino-1,3,5-triazine hybrids.

This article reports for the first time the synthesis of some novel ß-lactam morpholino-1,3,5-triazine hybrids by a [2+2]-cycloaddition reaction of imines 7a-c, 9a-c and 11 with ketenes derived from substituted acetic acids. The reaction was totally diastereoselective, leading exclusively to the formation of cis-ß-lactams 8a-l, 10a-f and 12a-c. The synthesized compounds were tested for activity towards SW1116, MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. None of the compounds exert an observable effect on HepG2, MCF-7 and HEK-293 cells, but compounds 7b, 8f, 8g, 8l, 10c, and 10e exhibited excellent growth inhibitory activity (IC50 < 5 µM) against SW 1116 cells, comparable to that of doxorubicin (IC50 = 6.9 µM). An evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 7b, 9a, 9b and 9c have strong free radical scavenging activity. UV absorption titration studies reveal that 7b, 8l, 8g and 8f interact strongly with calf-thymus DNA (CT-DNA) in the order of 8l > 7b > 8f > 8g. Collectively, the in vitro capabilities of some of these morpholino-triazine imines and ß-lactams suggest possible applications to development of new antioxidants and DNA binding therapeutics.

Benzoin 4-ethylthiosemicarbazone.

In the title compound, 2-hydroxy-1,2-diphenylethanone 4-ethylthiosemicarbazone, C17H19N3OS, the thiosemicarbazone moiety is planar and has an E configuration. The planar phenyl rings make dihedral angles of 82.34 (8) and 8.07 (17) degrees with the plane of the thiosemicarbazone moiety. The crystal structure contains two intramolecular (N-H...O and N-H...N) and one intermolecular interaction (O-H...S), as well as two C-H...pi(benzene) interactions. Molecules are stacked in columns running along the a axis. Molecules in each column are connected to each other by means of linear O-H...S hydrogen bonds and C-H...pi interactions. In addition, there are also C-H...pi(benzene) interactions between the columns.