Evaluation of Transition Metal Complexes of Benzimidazole-Derived Scaffold as Promising Anticancer Chemotherapeutics

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 5; p. 1232
• Main Authors: Hussain, Afzal, AlAjmi, Mohamed F, Rehman, Md Tabish, Khan, Azmat Ali, Shaikh, Perwez Alam, Khan, Rais Ahmad
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.05.2018; MDPI
• Subjects: Aminobenzimidazole; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Benzimidazoles; Benzimidazoles - chemical synthesis; Benzimidazoles - pharmacology; Biotechnology; Calf thymus; Cancer; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Cell death; Cell Line, Tumor; cell migration/adhesion; Cell Movement - drug effects; Cell Survival - drug effects; Cobalt - chemistry; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Copper; Copper - chemistry; Crystallography; Crystallography, X-Ray; cytotoxicity; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA binding/cleavage; DNA Cleavage; Drug Screening Assays, Antitumor; Female; Free Radical Scavengers - chemistry; Humans; In vivo methods and tests; Ligands; Male; Metal complexes; Mice; Molecular Structure; Necrosis; Nuclease; Structure-Activity Relationship; Toxicity; toxicity profile; Transition metal compounds; Tumor cell lines; X-ray crystallography; Zinc; Zinc - chemistry; metal complexes; cell migration/adhesion; DNA binding/cleavage; apoptosis; toxicity profile; cytotoxicity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23051232

Three new transition metal complexes, Cu(II) , Co(II) , and Zn(II) with ligand “bimnap” derived from 1-methyl-2-aminobenzimidazole and 2-hydroxynapthaldehyde were synthesized and characterized. The structure of the ligand was determined by single X-ray crystallography. All the three complexes, ⁻ were examined for the mode of interaction with biomolecule viz., calf thymus-DNA (CT-DNA) using various spectroscopic methods. The nuclease activity was performed against pBR322 DNA that exhibited concentration-dependent degradation of the nucleic acid. The mechanism of DNA cleavage was studied by the electrophoretic pattern in the presence of the radical scavengers. Also, the complexes ⁻ were analyzed for groove binding affinity. Moreover, in vitro cytotoxicities of the complexes ⁻ were tested against the five human cancer cell lines, i.e., HeLa, SK-MEL-1, HepG2, HT108, and MDA-MB 231. Also, the cell adhesion and migration properties upon treatment of cell lines with complexes ⁻ and consequently, their cell death pathway via apoptosis and necrosis were analyzed. Further, complexes ⁻ were studied in vivo for their toxicities and tolerabilities in mice. In sum, the complexes ⁻ showed merits of an effective anticancer agent in cell lines⁻based study while minor side effects were observed in vivo.A green solvent extraction technology involving a microwave processing method was used to increase the content of minor ginsenosides from . This article aims to investigate the optimization of preparation of the minor ginsenosides by this microwave processing method using single-factor experiments and response surface methodology (RSM), and discuss the blood-enriching activity and hemostatic activity of the extract of microwave processed (EMPN) The RSM for production of the minor ginsenosides was based on a three-factor and three-level Box-Behnken design. When the optimum conditions of microwave power, temperature and time were 495.03 W, 150.68 °C and 20.32 min, respectively, results predicted that the yield of total minor ginsenosides ( ₉) would be 93.13%. The actual value of ₉ was very similar to the predicted value. In addition, the pharmacological results of EMPN in vivo showed that EMPN had the effect of enriching blood in -acetylphenylhydrazine (APH) and cyclophosphamide (CTX)-induced blood deficient mice because of the increasing content of white blood cells (WBCs) and hemoglobin (HGB) in blood. Hemostatic activity in vitro of EMPN showed that it had significantly shortened the clotting time in PT testing ( 0.05). The hemostatic effect of EMPN was mainly caused by its components of Rh₄, 20( )-Rg₃ and 20( )-Rg₃. This microwave processing method is simple and suitable to mass-produce the minor ginsenosides from .