Search results for "drug discovery"

Chrysophanol- and nepodin-8-O-β-D-glucopyranoside from Rumex acetosella, the cytotoxicity towards drug sensitive and multi- drug resistant T leukaemi…

2016

Synthesis of Thymoquinone–Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents

2017

[Image: see text] A series of hybrid compounds based on the natural products artemisinin and thymoquinone was synthesized and investigated for their biological activity against the malaria parasite Plasmodium falciparum 3D7 strain, human cytomegalovirus (HCMV), and two leukemia cell lines (drug-sensitive CCRF-CEM and multidrug-resistant subline CEM/ADR5000). An unprecedented one-pot method of selective formation of C-10α-acetate 14 starting from a 1:1 mixture of C-10α- to C-10β-dihydroartemisinin was developed. The key step of this facile method is a mild decarboxylative activation of malonic acid mediated by DCC/DMAP. Ether-linked thymoquinone–artemisinin hybrids 6a/b stood out as the most…

N-Desmethyldauricine Induces Autophagic Cell Death in Apoptosis-Defective Cells via Ca2+ Mobilization

2017

Resistance of cancer cells to chemotherapy remains a significant problem in oncology. Mechanisms regulating programmed cell death, including apoptosis, autophagy or necrosis, in the treatment of cancers have been extensively investigated over the last few decades. Autophagy is now emerging as an important pathway in regulating cell death or survival in cancer therapy. Recent studies demonstrated variety of natural small-molecules could induce autophagic cell death in apoptosis-resistant cancer cells, therefore, discovery of novel autophagic enhancers from natural products could be a promising strategy for treatment of chemotherapy-resistant cancer. By computational virtual docking analysis,…

Generalized Molecular Descriptors Derived From Event-Based Discrete Derivative.

2016

In the present study, a generalized approach for molecular structure characterization is introduced, based on the relation frequency matrix (F) representation of the molecular graph and the subsequent calculation of the corresponding discrete derivative (finite difference) over a pair of elements (atoms). In earlier publications (22- 24), an unique event, named connected subgraphs, (based on the Kier-Hall's subgraphs) was systematically employed for the computation of the matrix F. The present report is a generalization of this notion, in which eleven additional events are introduced, classified in three categories, namely, topological (terminal paths, vertex path incidence, quantum subgrap…

An overview of recent molecular dynamics applications as medicinal chemistry tools for the undruggable site challenge

2018

Molecular dynamics (MD) has become increasingly popular due to the development of hardware and software solutions and the improvement in algorithms, which allowed researchers to scale up calculations in order to speed them up. MD simulations are usually used to address protein folding issues or protein-ligand complex stability through energy profile analysis over time. In recent years, the development of new tools able to deeply explore a potential energy surface (PES) has allowed researchers to focus on the dynamic nature of the binding recognition process and binding-induced protein conformational changes. Moreover, modern approaches have been demonstrated to be effective and reliable in …

Substrate Specificity of Aglaia loheri Active Isolate towards P-glycoprotein in Multidrug-Resistant Cancer Cells

2016

Multidrug resistance (MDR) is a major contributory factor in the failure of chemotherapy. Concrete interpretation of P-glycoprotein (P-gp) substrate specificity, whether a substance is a substrate or an inhibitor, represents an important feature of a compound's pharmaceutical profiling in drug design and development. In this work, the P-gp substrate specificity of Maldi 531.2[M+H]+, a phenol ester from Aglaia loheri Blanco leaves was investigated. This study focuses on the effect of Maldi 531.2[M+H]+ on P-gp ATPase activity, which was examined by measuring the amount of inorganic phosphates (Pi) released as a result of ATP hydrolysis. To test the effects of Maldi 531.2[M+H]+ on MDR activit…

Editorial (Thematic Issue: Myokines and Exercise Training: More Shadows than Lights).

2016

Potential Phytopharmacy and Food Applications of Capsicum spp.: A Comprehensive Review

2018

Capsicum genus (Solanaceae) is native to the Americas. Today, it is an important agricultural crop cultivated around the world, not only due to its economic importance, but also for the nutritional value of the fruits. Among their phytochemical constituents, capsaicinoids are characteristic and responsible of the pungency of sharp-tasting cultivars. Moreover, Capsicum and capsaicinoids (mainly, capsaicin) have been largely studied because of their health benefits. Thus, this study reviews the scientific knowledge about Capsicum spp. and their phytochemicals against cancer, diabetes, gastrointestinal diseases, pain, and metabolic syndrome, as well as their antioxidant and antimicrobial acti…

New perspectives for natural triterpene glycosides as potential adjuvants.

2017

Abstract Background Triterpene glycosides are a vast group of secondary metabolites widely distributed in plants including a high number of biologically active compounds. The pharmacological potential is evaluated by using many bioassays particularly in the field of cancerology, immunology, and microbiology. The adjuvant concept is well known for these molecules in vaccines, but there is little preclinical evidence to support this concept in the management of cancer, infections and inflammation. Purpose We aim to review some examples of triterpene glycosides from natural sources which exhibit adjuvant activity when they are co-adminitered with anticancer drugs, targeted toxins, antimicrobia…

Detection of Vasodilators From Herbal Components by a Transcriptome-Based Functional Gene Module Reference Approach

2019

Vasodilatation is one of the key therapeutic strategies for the treatment of various cardiovascular diseases with high blood pressure. Therefore, development of drugs assisting blood vessel dilation is promising. It has been proved that many drugs display definite vasorelaxant effects. However, there are very few studies that systemically explore the effective vasodilators. In this work, we build a transcriptome-based functional gene module reference approach for systematic pursuit of agents with vasorelaxant effects. We firstly curate two functional gene modules that specifically involved in positive and negative regulation of vascular diameter based on the known gene functional interactio…