The zebrafish ( Danio rerio ) is used as an embryonic and larval model to perform in vitro experiments and developmental toxicity studies. Zebrafish may be used to determine the toxicity of samples in early screening assays, often in a high-throughput manner. The zebrafish embryotoxicity model is at the leading edge of toxicology research due to the short time required for analyses, transparency of embryos, short life cycle, high fertility, and genetic data similarity. Zebrafish toxicity studies range from assessing the toxicity of bioactive compounds or crude extracts from plants to determining the optimal process. Most of the studied extracts were polar, such as ethanol, methanol, and aqueous solutions, which were used to detect the toxicity and bioactivity. This review examines the latest research using zebrafish as a study model and highlights its power as a tool for detecting toxicity of medicinal plants and its effectiveness at enhancing the understanding of new drug generation. The goal of this review was to develop a link to ethnopharmacological zebrafish studies that can be used by other researchers to conduct future research.

Makaleyi görüntüle

It is over 50 years since the discovery of microtubules, and they have become one of the most important drug targets for anti-cancer therapies. Microtubules are predominantly composed of the protein tubulin, which contains a number of different binding sites for small-molecule drugs. There is continued interest in drug development for compounds targeting the colchicine-binding site of tubulin, termed colchicine-binding site inhibitors (CBSIs). This review highlights CBSIs discovered through diverse sources: from natural compounds, rational design, serendipitously and via high-throughput screening. We provide an update on CBSIs reported in the past three years and discuss the clinical status of CBSIs. It is likely that efforts will continue to develop CBSIs for a diverse set of cancers, and this review provides a timely update on recent developments.

Makaleyi görüntüle

The mammalian or mechanistic target of rapamycin (mTOR) and associated phosphatidyl-inositiol 3-kinase (PI3K)/protein kinase B (Akt) pathways regulate cell growth, differentiation, migration, and survival, as well as angiogenesis and metabolism. Dysregulation of these pathways is frequently associated with genetic/epigenetic alterations and predicts poor treatment outcomes in a variety of human cancers including cutaneous malignancies like melanoma and non-melanoma skin cancers. Recently, the enhanced understanding of the molecular and genetic basis of skin dysfunction in patients with skin cancers has provided a strong basis for the development of novel therapeutic strategies for these obdurate groups of skin cancers. This review summarizes recent advances in the roles of PI3K/Akt/mTOR and their targets in the development and progression of a broad spectrum of cutaneous cancers and discusses the current progress in preclinical and clinical studies for the development of PI3K/Akt/mTOR targeted therapies with nutraceuticals and synthetic small molecule inhibitors.

Makaleyi görüntüle

Privileged structures have been widely used as an effective template in medicinal chemistry for drug discovery. Chalcone is a common simple scaffold found in many naturally occurring compounds. Many chalcone derivatives have also been prepared due to their convenient synthesis. These natural products and synthetic compounds have shown numerous interesting biological activities with clinical potentials against various diseases. This review aims to highlight the recent evidence of chalcone as a privileged scaffold in medicinal chemistry. Multiple aspects of chalcone will be summarized herein, including the isolation of novel chalcone derivatives, the development of new synthetic methodologies, the evaluation of their biological properties, and the exploration of the mechanisms of action as well as target identification. This review is expected to be a comprehensive, authoritative, and critical review of the chalcone template to the chemistry community.

Makaleyi görüntüle

This work assesses the current instrumentation, method development, and applications in countercurrent chromatography (CCC) and centrifugal partition chromatography (CPC), collectively referred to as countercurrent separation (CCS). The article provides a critical review of the CCS literature from 2007 since our last review (J. Nat. Prod. 2008, 71, 1489-1508), with a special emphasis on the applications of CCS in natural products research. The current state of CCS is reviewed in regard to three continuing topics (instrumentation, solvent system development, theory) and three new topics (optimization of parameters, workflow, bioactivity applications). The goals of this review are to deliver the necessary background with references for an up-to-date perspective of CCS, to point out its potential for the natural product scientist, and thereby to induce new applications in natural product chemistry, metabolome, and drug discovery research involving organisms from terrestrial and marine sources.

Makaleyi görüntüle