Synthesis and Biological Evaluation of Structurally Diverse Benzimidazole Scaffolds as Potential Chemotherapeutic Agents.

BACKGROUND AND OBJECTIVE: Drug resistance and adverse effects are immense healthcare challenges in cancer therapy. Benzimidazole ring-based small molecules have been effective anticancer agents in drug development. In an effort to develop novel chemotherapeutics, we synthesized and assessed the anticancer and antibacterial activities of a small library of structurally unique benzimidazoles. METHODS: The benzimidazoles were derived from indole, N-alkyl indole, fatty acid, and alpha-amino acid scaffolds providing a panel of diverse structures. The compounds were tested in three different cancer cell lines for cytotoxicity: HepG2 (human hepatocellular carcinoma), HeLa (human cervical carcinoma), and A549 (human lung carcinoma). Mechanism of cell death induced by benzimidazoles was evaluated using fluorescent dye-based apoptosis-necrosis assay, immunoblotting for active caspases, topoisomerase-II activity assay, and cell cycle assay. RESULTS: Cell viability testing revealed that indole- and fatty acid-based benzimidazoles were most potent followed by the amino acid derivatives. Many compounds induced cytotoxicity in a concentration-dependent manner with cellular cytotoxicity (CC50) <20µM in the cell lines tested. Most compounds exhibited cytotoxicity via apoptosis through the intrinsic pathway. Inhibition of topoisomerase activity and cell cycle alterations were not the primary mechanisms of cytotoxicity. In addition, several compounds showed promising activity against S. aureus and S. epidermidis (Minimum Inhibitory Concentration (MIC) of as low as 0.04µmol/mL). CONCLUSION: The reported benzimidazole derivatives possess promising anticancer and antibacterial properties. Additionally, we discovered apoptosis to be the primary mechanism for cancer cell death induced by the tested benzimidazoles. Our findings suggest that further development of these scaffolds could provide drug leads towards new chemotherapeutics.

An expressive-arts-based life-death education program for the elderly: A qualitative study.

This study endeavors to investigate how healthcare workers, equipped with expressive arts methods, could foster life-death education for the elderly. Forty-nine older adults aged 60 or above joined a 10-session expressive arts-based life-death education program that was led by social workers equipped with expressive arts methods. An ethnographic research approach, with a post-treatment focus group (n = 17), was conducted with the participants. The results showed that expressive arts methods could enhance reorganization of life experiences, promote dealing with ambivalent emotion regarding life-death issues, improve communicating life-death issues with family members, and induce ideas to prepare for death.

Performance study of vegetated sequencing batch coal slag bed treating domestic wastewater in suburban area.

A practical and affordable wastewater treatment system serving small community in suburban areas was studied. The system was a vegetated sequencing batch coal slag bed integrated with the rhythmical movement of wastewater and air like that of a sequencing batch reactor. The removal mechanisms capitalized on the pollutant removal process in conventional constructed wetland. Cyperus alternifolius was planted into the coal slag bed to form a novel plant-soil-microbial interactive system. Nutrients in the domestic wastewater, which cause environmental nuisance like eutrophication, were targeted to be eliminated by the process design. Operated with the contact time of 18 h, the treatment systems achieved around 60% removal efficiency for carbonaceous matters. The removals of ammonia nitrogen and phosphorus were about 50% and 40%, respectively, while the removal of total suspended solids was approaching 80%. From the current study, the construction cost of the vegetated sequencing batch coal slag bed was 256 RMB/m3 and the operation cost was 0.13 RMB/m3. With the advantages of ease of operation, low costs, desirable treatment efficiency and aesthetic value, the vegetated sequencing batch coal slag bed is proposed to be an alternative for onsite domestic wastewater treatment in suburban areas.

Nutrient release and sediment oxygen demand in a eutrophic land-locked embayment in Hong Kong.

Tolo Harbour is a large eutrophic land-locked estuarine embayment in Hong Kong. The rapid urbanization, commercio-industrial activities and lack of legislative control around the Tolo catchment produced large quantities of untreated or partially treated municipal sewage, agricultural wastes and cottage industrial effluents which were discharged into Tolo Harbour via rivers and watercourses. Control measures were implemented to reduce the external nutrient loading into the harbour since the early 1980s. Nutrient data for the period 1982 to 1997 were analyzed for temporal trends. Over the period of observation, the total inorganic nitrogen and total phosphorus both show an increasing trend, despite a decade of efforts in reducing nutrient loading. The release rates of potentially mobile nitrogen (N) and phosphorus (P) from the sediments collected from Tolo Harbour were determined by N and P release experiments under oxic conditions. The experimental results showed that the sediment released significant amount of nutrients, especially orthophosphates and ammonia nitrogen. The maximum release rates were 15.0 and 206.0 mg/m2/day, respectively. Although the external nutrient loading has been reduced, nutrients could gradually be released back into the water column from the contaminated sediments and delay improvement of the water quality.

Some cellular characteristics of somatostatin neurons and terminals in the periventricular nucleus of the rat hypothalamus and median eminence. Electron microscopic immunohistochemistry.

Somatostatin neuronal perikarya and their processes, presumably dendrites, in the periventricular nucleus of the rat hypothalamus and terminals in the median eminence were observed by electron microscopic immunohistochemistry. Neuronal perikarya and processes contained immunoreactive dense granules (100-120 nm in diameter) and other cellular components such as polysomes, rER membranes occasionally showed high electron density. Few axo-somatic terminals were found on the somatostatin neurons, but we could detect a number of preterminal axons on immunoreactive processes, presumably dendrites. Therefore, we considered that somatostatin neurons receive mainly neuronal input through axo-dendritic synapses rather than through axo-somatic ones. In the somatostatin terminals in the external layer of the median eminence immunoreactivity was completely restricted on the granules.

The location of LH-RH neurons in the rat hypothalamus and their pathways to the median eminence. Experimental immunohistochemistry and radioimmunoassay.

The location of the perikarya of LH-RH neurons in the rat hypothalamus and their pathways to the median eminence were studied by immunohistochemistry and radioimmunoassay after placing stereotaxic electrolytic lesions in several parts of the hypothalamus. The principal location of the cell somata was found to be in the ventral part of the medial preoptic area; their pathways were classified into a main baso-lateral pathway and an accessory descending pathway branching off from the former. The main pathway was found to cross in the vicinity of the corresponding neuronal perikarya. The central median eminence and the dorsal and ventral walls of the tubero-infundibular sulcus of the caudal part of the median eminence are innervated mainly by the baso-lateral pathway. On the other hand, the rostral and most caudal protions of the median eminence are innervated principally by the descending pathway and have a subsidiary dual innervation. The projection of LH-RH neurons to the OVLT is believed to originate from perikarya adjacent to this circumventricular organ.

Detection of catecholamine and luteinizing hormone-releasing hormone (LH-RH) containing nerve endings in the median eminence and the organon vasculosum laminae terminalis by fluorescence histochemistry and immunohistochemistry on the same microscopic sections.

Distribution of catecholamine (CA) and LH-RH nerve endings in the median eminence (ME) and the organon vasculosum laminae terminalis (OVLT) of the rat was investigated by application of fluorescence histochemistry and immunohistochemistry on the same sections of the tissue. In the ME, those two kinds of endings coexisted in the lateral portion of the middle part of ME, and in the wall of tuberoinfundibular sulcus, where they might be considered to have functional correlation. In the OVLT they were also distributed in fairly near distance, but they were not so closely associated as observed in the ME.