9 research outputs found
In Vivo Evaluation of the Nitroimidazole-Based Thioflavin-T Derivatives as Cerebral Ischemia Markers
Timely imaging and accurate interpretation of cerebral ischemia are required to
identify patients who might benefit from more aggressive therapy, and nuclear medicine
offers a noninvasive method for demonstrating cerebral ischemia. Three
nitroimidazole-based thioflavin-T derivatives, N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl) propanamide (4NPBTA), N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl)-N-methylpropanamide (4NPBTA-1), and
N-[4-(benzothiazol-2-yl)phenyl]-3-(2-nitroimidazole-1-yl) propanamide (2NPBTA), were
radioiodinated and evaluated as possible cerebral ischemia markers. In normal mice,
these compounds showed good permeation of the intact blood-brain barrier (BBB), high
initial brain uptake, and rapid washout. In gerbil stroke models that had been subjected
to right common carotid artery ligation to produce cerebral ischemia, [131I]2NPBTA,
uptake in the right cerebral hemisphere decreased more slowly than that of the left, and
the right/left hemisphere uptake ratios increased with time. Also, the right/left
hemisphere uptake ratios correlated positively with the severity of the stroke. The results showed that
[131I]2NPBTA had a specific location in the cerebral ischemic tissue. This represented a first step in finding new drugs and might provide a possible cerebral
ischemic marker
Radiolabelled Molecules for Brain Imaging with PET and SPECT
Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are in vivo molecular imaging methods which are widely used in nuclear medicine for diagnosis and treatment follow-up of many major diseases. These methods use target-specific molecules as probes, which are labeled with radionuclides of short half-lives that are synthesized prior to the imaging studies. These probes are called radiopharmaceuticals. The use of PET and SPECT for brain imaging is of special significance since the brain controls all the body’s functions by processing information from the whole body and the outside world. It is the source of thoughts, intelligence, memory, speech, creativity, emotion, sensory functions, motion control, and other important body functions. Protected by the skull and the blood–brain barrier, the brain is somehow a privileged organ with regard to nutrient supply, immune response, and accessibility for diagnostic and therapeutic measures. Invasive procedures are rather limited for the latter purposes. Therefore, noninvasive imaging with PET and SPECT has gained high importance for a great variety of brain diseases, including neurodegenerative diseases, motor dysfunctions, stroke, epilepsy, psychiatric diseases, and brain tumors. This Special Issue focuses on radiolabeled molecules that are used for these purposes, with special emphasis on neurodegenerative diseases and brain tumors
New methods for synthesis of substituted 2-phenylbenzothiazoles
In recent years, substituted 2-arylbenzothiazoles have emerged as an important pharmacophore with a number of possible diagnostic and therapeutic applications. An example of this is provided by the simple 2- 4- aminophenyl benzothiazole series which has shown both exquisite antitumour activity and potential as a PET tracer in non-invasive imaging of Alzheimer's disease. Although there are documented procedures for their synthesis, the majority refer to those benzothiazoles unsubstituted in the benzothiazole ring and involve the use of harsh reaction conditions, and chromatographic purification. In this work a simple method for the rapid access to a range of 2- phenylbenzothiazoles both substituted and unsubstituted in the benzothiazole ring is reported, importantly the method described requires no chromatographic purification. A simple one-step synthesis to 2-phenylbenzothiazoles unsubstituted in the benzothiazole ring is described whereby the desired product was made in high yield and with a short reaction time under either thermal or microwave irradiation of a variety of benzaldehydes and 2-aminothiophenol using sodium metabisulfite as a mild oxidant in DMSO. The methodology was extended to the synthesis of biologically relevant 2- phenylbenzothiazoles substituted on the benzothiazole ring, starting from the appropriately substituted 2-aminophenyldisulfide. Under thermal conditions, a small diverse library of compounds was obtained in short reaction times with no chromatographic purification necessary. The synthesis of a number of 2-phenylbenzothiazoles either substituted or unsubstituted in the benzothiazole ring is also reported by polymer-supported synthesis, utilising polymer-supported triphenylphosphine and p- toluenesulfonic acid as catalysts for the reaction. Biological evaluation was undertaken on four cancer cell lines, namely, A549, LoVo, MCF-7, and PC3, with A549 and MCF-7 the most active. Although no exquisite activity was found, as these compounds contain either or both a carbon and fluorine atom they have the possibility to be labelled with either a 1 C or 18F label and therefore have potential use in PET imaging
Anti-angiogenic and toxicity effects of Derris trifoliata extract in zebrafish embryo
Introduction: Derris trifoliata has been traditionally used as folk for the treatment of , rheumatic joints, diarrhoea, and dysmenorrhea, and rotenoids isolated from the plant have shown to exhibit anti-cancer properties. This study aimed to assess the toxicity effects and antiangiogenic activity of extract of Derris trifoliata on zebrafish embryo model.
Materials and Methods: Zebrafihs embryos were treated with aqueous extract of Derris Trifoliata to evaluate its effects on angiogenesis and zebrafish-toxicity. Angiogenic response was analyzed using whole-mount alkaline phosphatase (AP) vessel staining on 72 hours post fertilization (hpf) zebrafish embryos.
Results: 1.0 mg/ml concentration was toxic to zebrafish embryos and embryos exposed to concentrations at 0.5 mg/ml and below showed some malformations. Derris trifoliata aqueous extract also showed some anti-angiogenic activity in vivo in the zebrafish embryo model wereby at high concentration inhibited vessel formation in zebrafish embryo.
Conclusions: The anti-angiogenic response of extract of Derris trifoliata in zebrafish in vivo model suggest its therapeutic potential as anti-cancer agent