Current Medicinal Chemistry - Volume 27, Issue 36, 2020

Chemotherapy resistance is a rising concern in Gastric Cancer (GC) and has led to the investigation of various cellular compounds. functional equilibrium of histone acetylation and deacetylation was discovered in all cells, regulated by Histone Acetyltransferases and Deacetylases (HDACs), controlling chromatin coiling status and changing gene expression appropriately. In accordance with recent research, this equilibrium can be dysregulated in cancer cells aiding in the process of carcinogenesis and tumor progression by altering histone and non-histone proteins affecting gene expression, cell cycle control, differentiation, and apoptosis in various malignancies. In addition, increased HDAC expression in GC cells has been associated with increased stage, tumor invasion, nodal metastases, increased distant metastatic potential, and decreased overall survival. HDAC inhibitors could be used as treatment regimens for GC patients and could develop important synergistic interactions with chemotherapy drugs. The aim of this article is to review the molecular identity and mechanism of action of HDAC inhibitors, as well as highlight their potential utility as anti-cancer agents in GC.

The development of new medical cancer treatment technologies is of great significance in reducing cancer mortality. Traditional clinical cancer therapy has a short drug action time, difficulty in accurately targeting tumour tissues and high levels of toxicity in normal tissues. With the development of nanotechnology, nanomaterials have been used as drug carriers to specifically target cancer cells and release drugs into the tumour environment. This technique has become an important research hotspot in cancer treatment. There are several advantages of using nanomaterials for cancer treatment that improve the efficacy of drug delivery, including increased drug concentrations in the targeted tumour area, reduced toxicity in normal tissues and controlled drug release. In this work, we describe the latest research development on the use of nanomaterials for drug delivery in cancer treatment and explore related mechanistic pathways. In addition, the methods used to control drug release into the targeted area using nanocarriers are reviewed in detail. Overall, we present current achievements using nanomaterials and nanotechnologies in cancer treatment, followed by current challenges and future prospects.

Background: Gonadotropin-Releasing Hormone (GnRH) is a key element in sexual maturation and regulation of the reproductive cycle in the human organism. GnRH interacts with the pituitary cells through the activation of the Gonadotropin Releasing Hormone Receptors (GnRHR). Any impairments/dysfunctions of the GnRH-GnRHR complex lead to the development of various cancer types and disorders. Furthermore, the identification of GnRHR as a potential drug target has led to the development of agonist and antagonist molecules implemented in various treatment protocols. The development of these drugs was based on the information derived from the functional studies of GnRH and GnRHR. Objective: This review aims at shedding light on the versatile function of GnRH and GnRH receptor and offers an apprehensive summary regarding the development of different agonists, antagonists and non-peptide GnRH analogues. Conclusion: The information derived from these studies can enhance our understanding of the GnRH-GnRHR versatile nature and offer valuable insight into the design of new more potent molecules.

DNA methylation is considered as a crucial part of epigenetic modifications and a popular research topic in recent decades. It usually occurs with a methyl group adding to the fifth carbon atom of cytosine while the base sequence of DNA remains unchanged. DNA methylation has significant influences on maintaining cell functions, genetic imprinting, embryonic development and tumorigenesis procedures and hence the analysis of DNA methylation is of great medical significance. With the development of analytical techniques and further research on DNA methylation, numerous DNA methylation detection strategies based on biosensing technology have been developed to fulfill various study requirements. This article reviewed the development of electrochemistry and optical biosensing analysis of DNA methylation in recent years; in addition, we also reviewed some recent advances in the detection of DNA methylation using new techniques, such as nanopore biosensors, and highlighted the key technical and biological challenges involved in these methods. We hope this paper will provide useful information for the selection and establishment of analysis of DNA methylation.

Background: Spectroscopic imaging based on the spontaneous Raman scattering effects can provide unique fingerprint information in relation to the vibration bands of molecules. Due to its advantages of high chemical specificity, non-invasive detection capability, low sensitivity to water, and no special sample pretreatment, Raman Spectroscopic Imaging (RSI) has become an invaluable tool in the field of biomedicine and medicinal chemistry. Methods: There are three methods to implement RSI, including point scanning, line scanning and wide-field RSI. Point-scanning can achieve two-and three-dimensional imaging of target samples. High spectral resolution, full spectral range and confocal features render this technique highly attractive. However, point scanning based RSI is a time-consuming process that can take several hours to map a small area. Line scanning RSI is an extension of point scanning method, with an imaging speed being 300-600 times faster. In the wide-field RSI, the laser illuminates the entire region of interest directly and all the images then collected for analysis. In general, it enables more accurate chemical imaging at faster speeds. Results: This review focuses on the recent advances in RSI, with particular emphasis on the latest developments on instrumentation and the related applications in biomedicine and medicinal chemistry. Finally, we prospect the development trend of RSI as well as its potential to translation from bench to bedside. Conclusion: RSI is a powerful technique that provides unique chemical information, with a great potential in the fields of biomedicine and medicinal chemistry.

Background: The management of pain in patients with rheumatoid arthritis (RA) is a complex subject due to the autoimmune nature of the pathology. Studies have shown that chemical mediators play a fundamental role in the determination, susceptibility and modulation of pain at different levels of the central and peripheral nervous system, resulting in interesting novel molecular targets to mitigate pain in patients with RA. However, due to the complexity of pain physiology in RA cand the many chemical mediators, the results of several studies are controversial. Objective: The aim of this study was to identify the chemical mediators that are able to modulate pain in RA. Method: In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation index for studies that evaluated the expression of chemical mediators on the modulation of pain in RA. Results: Few studies have highlighted the importance of the expression of some chemical mediators that modulate pain in patients with rheumatoid arthritis. The expression of TRPV1, ASIC-3, and TDV8 encode ionic channels in RA and modulates pain, likewise, the transcription factors in RA, such as TNFα, TGF-β1, IL-6, IL-10, IFN-γ, IL-1b, mTOR, p21, caspase 3, EDNRB, CGRPCALCB, CGRP-CALCA, and TAC1 are also directly involved in pain perception. Conclusion: The expression of all chemical mediators is directly related to RA and the modulation of pain by a complex intra and extracellular signaling pathway, however, transcription factors are involved in modulating acute pain, while the ionic channels are involved in chronic pain in RA.

Licorice (Glycyrrhiza glabra L.) is widely regarded as an important medicinal plant and has been used for centuries in traditional medicine because of its therapeutic properties. Studies have shown that metabolites isolated from licorice have many pharmacological activities, such as antiinflammatory, anti-viral, participation in immune regulation, anti-tumor and other activities. This article gives an overview of the pharmacological activities and mechanisms of licorice metabolites and the adverse reactions that need attention. This review helps to further investigate the possibility of licorice as a potential drug for various diseases. It is hoped that this review can provide a relevant theoretical basis for relevant scholars’ research and their own learning.

Microorganisms obtained from the deep sea are a rich source of marine natural products with distinctive chemical structures and bioactivities. In this review, we will provide a retrospective of outstanding research within the scope of deep-sea (≥1000 m) microbial natural products, which has produced up to 442 compounds by the end of 2017. Approximetely, 60% of these structures have demonstrated various biological activities with more than 30% showing cytotoxic function. In this review, we particularly summarize those successful research on secondary metabolites produced by deep-sea derived microorganisms with inclusion of structural characteristics, biological activities, together with biogenetic origins and taxonomic features of the source microorganisms, from which, we expect to provide more comprehensive understanding of small molecules obtained from deep-sea environment and benefit the ongoing scholarly endeavors in the search for novel pharmaceutical agents from the deep-sea derived microorganisms.