Synthesis and evaluation of 2-aryl-1H-benzo[d]imidazole derivatives as potential microtubule targeting agents.

Microtubule targeting agents (MTAs) are the potential drug candidates for anticancer drug discovery. Disrupting the microtubule formation or inhibiting the de-polymerization process by a synthetic molecule can lead to an excellent anticancer drug candidate. Here, we present the 2,5-substituted-1H-benzo[d]imidazole derivatives as potential colchicine, nocodazole binding site targeting agents. About 20 benzimidazole derivatives were synthesized with 82.0%-94.0% yield using mild reaction conditions. The synthesized compounds showed moderate to excellent anticancer activity established in three cell lines, including Hela cells, A549 cells, MRC-5 cells. The compounds B15, B16, B19, and B20 are the potential candidates with the IC50 values <15 µM in the three different cell lines. In MTT assay, compounds B15, B16, B19, and B20 showed excellent antiproliferation activity indicated by IC50 values in the range of 5.3 ± 0.21 to 18.1 ± 0.32 µM using HeLa and A549 cell lines. The predicted absorption, distribution, metabolism and excretion (ADME) properties and drug-likeness properties of B15, B16, B19, and B20 indicate that these compounds can be used as lead compounds for further study to develop excellent MTAs.

An abiotic fluorescent probe for the detection and quantification of carcinoembryonic antigen.

The reported methods mainly use biomolecules such as antibodies, enzymes, and aptamers for biomarker detection. However, applying an abiotic fluorescent probe to detect cancer biomarkers such as carcinoembryonic antigen (CEA) has not been reported. In this regard, we conceived an abiotic fluorescent probe BIQ-1 for the rapid yet straightforward detection of CEA. The bioinformatics tools and molecular docking techniques were used to develop the probe BIQ-1 for the selective detection and quantification of CEA in a buffer matrix resembling serum. The probe BIQ-1 exhibited a limit of detection of 0.2 ng/mL for CEA in a simple cuvette-based experiment. The BIQ-1 did no show interference from the possible interfering components such as hemoglobin, intralipid, and human serum albumin (HSA) in concentrations several-fold higher (µg/mL) than CEA.

Macrocycles and Supramolecules as Antioxidants: Excellent Scaffolds for Development of Potential Therapeutic Agents.

Oxidative stress due to the high levels of reactive oxygen species (ROS) that damage biomolecules (lipids, proteins, DNA) results in acute inflammation. However, without proper intervention, acute inflammation progresses to chronic inflammation and then to several chronic diseases, including cancer, myocardial infarction, cardiovascular diseases, chronic inflammation, atherosclerosis, and more. There has been extensive research on the antioxidants of natural origin. However, there are myriad possibilities for the development of synthetic antioxidants for pharmacological applications. There is an increasing interest in the identification of novel synthetic antioxidants for the modulation of biochemical processes related to ROS. In this regard, derivatives of supramolecules, such as calix[n]arene, resorcinarene, calixtyrosol, calixpyrrole, cucurbit[n]uril, porphyrin etc. are gaining attention for their abilities to scavenge the free radicals. Supramolecular chemistry offers excellent scaffolds for the development of novel antioxidants that can be used to modulate free radical reactions and to improve the disorders related to oxidative stress. This review focuses on the interdisciplinary approach for the design and development of novel synthetic antioxidants based on supramolecular scaffolds, with potentially protective effects against oxidative stress.

Feasibility of Eye Tracking Assisted Vestibular Rehabilitation Strategy Using Immersive Virtual Reality.

OBJECTIVES: Even though vestibular rehabilitation therapy (VRT) using head-mounted display (HMD) has been highlighted recently as a popular virtual reality platform, we should consider that HMD itself do not provide interactive environment for VRT. This study aimed to test the feasibility of interactive components using eye tracking assisted strategy through neurophysiologic evidence. METHODS: HMD implemented with an infrared-based eye tracker was used to generate a virtual environment for VRT. Eighteen healthy subjects participated in our experiment, wherein they performed a saccadic eye exercise (SEE) under two conditions of feedback-on (F-on, visualization of eye position) and feedback-off (F-off, non-visualization of eye position). Eye position was continuously monitored in real time on those two conditions, but this information was not provided to the participants. Electroencephalogram recordings were used to estimate neural dynamics and attention during SEE, in which only valid trials (correct responses) were included in electroencephalogram analysis. RESULTS: SEE accuracy was higher in the F-on than F-off condition (P=0.039). The power spectral density of beta band was higher in the F-on condition on the frontal (P=0.047), central (P=0.042), and occipital areas (P=0.045). Beta-event-related desynchronization was significantly more pronounced in the F-on (-0.19 on frontal and -0.22 on central clusters) than in the F-off condition (0.23 on frontal and 0.05 on central) on preparatory phase (P=0.005 for frontal and P=0.024 for central). In addition, more abundant functional connectivity was revealed under the F-on condition. CONCLUSION: Considering substantial gain may come from goal directed attention and activation of brain-network while performing VRT, our preclinical study from SEE suggests that eye tracking algorithms may work efficiently in vestibular rehabilitation using HMD.