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Medicinal Research Reviews

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https://www.readbyqxmd.com/read/29095519/no-and-hno-donors-nitrones-and-nitroxides-past-present-and-future
#1
REVIEW
Catarina Oliveira, Sofia Benfeito, Carlos Fernandes, Fernando Cagide, Tiago Silva, Fernanda Borges
The biological effects attributed to nitric oxide ((•) NO) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age-related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N-O bond enabled the development of several classes of compounds with potential clinical interest, among which (•) NO and HNO donors, nitrones, and nitroxides are of particular importance...
November 2, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29064108/strategies-to-diversify-natural-products-for-drug-discovery
#2
REVIEW
Gang Li, Hong-Xiang Lou
Natural product libraries contain specialized metabolites derived from plants, animals, and microorganisms that play a pivotal role in drug discovery due to their immense structural diversity and wide variety of biological activities. The strategies to greatly extend natural product scaffolds through available biological and chemical approaches offer unique opportunities to access a new series of natural product analogues, enabling the construction of diverse natural product-like libraries. The affordability of these structurally diverse molecules has been a crucial step in accelerating drug discovery...
October 24, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28926101/the-metabolic-cross-talk-between-epithelial-cancer-cells-and-stromal-fibroblasts-in-ovarian-cancer-progression-autophagy-plays-a-role
#3
REVIEW
Chanitra Thuwajit, Alessandra Ferraresi, Rossella Titone, Peti Thuwajit, Ciro Isidoro
Cancer and stromal cells, which include (cancer-associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation...
September 19, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28902434/biologically-active-quinoline-and-quinazoline-alkaloids-part-i
#4
REVIEW
Xiao-Fei Shang, Susan L Morris-Natschke, Ying-Qian Liu, Xiao Guo, Xiao-Shan Xu, Masuo Goto, Jun-Cai Li, Guan-Zhou Yang, Kuo-Hsiung Lee
Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted tremendous attention from researchers worldwide since the 19th century. Over the past 200 years, many compounds from these two classes were isolated from natural sources, and most of them and their modified analogs possess significant bioactivities. Quinine and camptothecin are two of the most famous and important quinoline alkaloids, and their discoveries opened new areas in antimalarial and anticancer drug development, respectively...
September 13, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28862319/breakthroughs-in-modern-cancer-therapy-and-elusive-cardiotoxicity-critical-research-practice-gaps-challenges-and-insights
#5
REVIEW
Ping-Pin Zheng, Jin Li, Johan M Kros
To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune-based therapeutic modalities of anticancer treatment (the fifth modality), e...
September 1, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28834581/pyrrolo-2-3-d-pyrimidine-7-deazapurine-as-a-privileged-scaffold-in-design-of-antitumor-and-antiviral-nucleosides
#6
REVIEW
Pavla Perlíková, Michal Hocek
7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are important analogues of biogenic purine nucleosides with diverse biological activities. Replacement of the N7 atom with a carbon atom makes the five-membered ring more electron rich and brings a possibility of attaching additional substituents at the C7 position. This often leads to derivatives with increased base-pairing in DNA or RNA or better binding to enzymes. Several types of 7-deazapurine nucleosides with potent cytostatic or cytotoxic effects have been identified...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28759124/recent-advances-in-uveal-melanoma-treatment
#7
REVIEW
Beatriz Álvarez-Rodríguez, Alfonso Latorre, Christian Posch, Álvaro Somoza
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Recent advances in the understanding of molecular characteristics helped to determine which tumors are most likely to progress. About 50% of patients carrying genetic alterations such as chromosomal aberrations and mutations are at significant risk for metastatic disease of which the majority will succumb to UM within few months. Currently, there is no effective treatment for metastatic uveal melanoma, and we hope this review will encourage researchers and clinicians to work to find a better standard of care...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28759115/anti-muc1-aptamer-a-potential-opportunity-for-cancer-treatment
#8
REVIEW
Maryam Sadat Nabavinia, Aida Gholoobi, Fahimeh Charbgoo, Mahboobeh Nabavinia, Mohammad Ramezani, Khalil Abnous
Mucin 1 (MUC1) is a protein usually found on the apical surface of most normal secretory epithelial cells. However, in most adenocarcinomas, MUC1 is overexpressed, so that it not only appears over the entire cell surface, but is also shed as MUC1 fragments into the blood stream. These phenomena pinpoint MUC1 as a potential target for the diagnosis and treatment of cancer; consequently, interest has increased in MUC1 as a molecular target for overcoming cancer therapy challenges. MUC1 currently ranks second among 75 antigen candidates for cancer vaccines, and different antibodies or aptamers against MUC1 protein are proving useful for tracing cancer cells in the emerging field of targeted delivery...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28682452/mitochondrial-dysfunction-and-potential-anticancer-therapy
#9
REVIEW
Matilde E Lleonart, Robert Grodzicki, Dmitri M Graifer, Alex Lyakhovich
Mitochondrial dysfunction (MDF) has been identified as an important factor in various diseases ranging from neurological disorders, to diseases of the cardiovascular system and metabolic syndromes. MDF was also found in cancer as well as in cancer predisposition syndromes with defective DNA damage response (DDR) machinery. Moreover, a recent highlight arises from the detection of MDF in eukaryotic cells upon treatment with antibiotics. In this review, we focus on recent studies of MDF in pathological conditions with a particular emphasis on the effects of various classes of antibiotics on mitochondria...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28643862/tumor-angiogenesis-revisited-regulators-and-clinical-implications
#10
REVIEW
Roberto Ronca, Mohammed Benkheil, Stefania Mitola, Sofie Struyf, Sandra Liekens
Since Judah Folkman hypothesized in 1971 that angiogenesis is required for solid tumor growth, numerous studies have been conducted to unravel the angiogenesis process, analyze its role in primary tumor growth, metastasis and angiogenic diseases, and to develop inhibitors of proangiogenic factors. These studies have led in 2004 to the approval of the first antiangiogenic agent (bevacizumab, a humanized antibody targeting vascular endothelial growth factor) for the treatment of patients with metastatic colorectal cancer...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28643446/artemisinin-as-an-anticancer-drug-recent-advances-in-target-profiling-and-mechanisms-of-action
#11
REVIEW
Yin Kwan Wong, Chengchao Xu, Karunakaran A Kalesh, Yingke He, Qingsong Lin, W S Fred Wong, Han-Ming Shen, Jigang Wang
Artemisinin and its derivatives (collectively termed as artemisinins) are among the most important and effective antimalarial drugs, with proven safety and efficacy in clinical use. Beyond their antimalarial effects, artemisinins have also been shown to possess selective anticancer properties, demonstrating cytotoxic effects against a wide range of cancer types both in vitro and in vivo. These effects appear to be mediated by artemisinin-induced changes in multiple signaling pathways, interfering simultaneously with multiple hallmarks of cancer...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28586525/novel-therapeutic-clues-in-thyroid-carcinomas-the-role-of-targeting-cancer-stem-cells
#12
REVIEW
Alessandro Antonelli, Concettina La Motta
Thyroid carcinomas (TCs), the most common endocrine tumors, represent the eighth most common cancer diagnosed worldwide in both women and men. To treat these malignancies, several drugs are now available and a number of novel ones have been enrolling in clinical trials, addressing both oncogenic pathways in cancer cells and angiogenic pathways in tumor endothelial cells. However, their use is not devoid of serious toxicities and their efficacy is limited, being dependent on carcinoma typology and the occurrence of acquired resistance...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28586517/extracellular-vesicles-in-the-tumor-microenvironment-therapeutic-resistance-clinical-biomarkers-and-targeting-strategies
#13
REVIEW
L Han, J Xu, Q Xu, B Zhang, E W-F Lam, Y Sun
Numerous studies have proved that cell-nonautonomous regulation of neoplastic cells is a distinctive and essential characteristic of tumorigenesis. Two way communications between the tumor and the stroma, or within the tumor significantly influence disease progression and modify treatment responses. In the tumor microenvironment (TME), malignant cells utilize paracrine signaling initiated by adjacent stromal cells to acquire resistance against multiple types of anticancer therapies, wherein extracellular vesicles (EVs) substantially promote such events...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28510338/therapeutic-targeting-of-poly-adp-ribose-polymerase-1-parp1-in-cancer-current-developments-therapeutic-strategies-and-future-opportunities
#14
REVIEW
Jyotika Rajawat, Nidhi Shukla, Durga Prasad Mishra
Poly(ADP-ribose) polymerase-1 (PARP-1) plays a central role in numerous cellular processes including DNA repair, replication, and transcription. PARP interacts directly, indirectly or via PARylation with various oncogenic proteins and regulates several transcription factors thereby modulating carcinogenesis. Therapeutic inhibition of PARP is therefore perceived as a promising anticancer strategy and a number of PARP inhibitors (PARPi) are currently under development and clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the concept of synthetic lethality in cancer therapeutics...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28181261/the-search-for-potent-small-molecule-hdacis-in-cancer-treatment-a-decade-after-vorinostat
#15
REVIEW
Chiara Zagni, Giuseppe Floresta, Giulia Monciino, Antonio Rescifina
Histone deacetylases (HDACs) play a crucial role in the remodeling of chromatin, and are involved in the epigenetic regulation of gene expression. In the last decade, inhibition of HDACs came out as a target for specific epigenetic changes associated with cancer and other diseases. Until now, more than 20 HDAC inhibitors (HDACIs) have entered clinical studies, and some of them (e.g., vorinostat, romidepsin) have been approved for the treatment of cutaneous T-cell lymphoma. This review provides an overview of current knowledge, progress, and molecular mechanisms of HDACIs, covering a period from 2011 until 2015...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28084618/drugs-in-clinical-trials-for-alzheimer-s-disease-the-major-trends
#16
REVIEW
Sergey O Bachurin, Elena V Bovina, Aleksey A Ustyugov
Alzheimer's disease (AD) is characterized by a chronic and progressive neurodegenerative process resulting from the intracellular and extracellular accumulation of fibrillary proteins: beta-amyloid and hyperphosphorylated Tau. Overaccumulation of these aggregates leads to synaptic dysfunction and subsequent neuronal loss. The precise molecular mechanisms of AD are still not fully understood but it is clear that AD is a multifactorial disorder and that advanced age is the main risk factor. Over the last decade, more than 50 drug candidates have successfully passed phase II clinical trials, but none has passed phase III...
September 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28052344/understanding-the-molecular-mechanisms-of-the-interplay-between-herbal-medicines-and-gut-microbiota
#17
REVIEW
Jun Xu, Hu-Biao Chen, Song-Lin Li
Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs...
September 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28029167/drug-mediated-regulation-of-glycosaminoglycan-biosynthesis
#18
REVIEW
Giancarlo Ghiselli
Glycosaminoglycans (GAGs) are a heterogeneous family of unbranched polysaccharides that exist in either a free state or attached to proteins and are found on the cell surface as well as in the extracellular matrix. GAGs play essential roles in cellular and tissue homeostasis, and their metabolism is altered in response to several pathological conditions. Despite strong experimental evidence supporting the function of GAGs in various diseases, little is known about the regulation of GAG biosynthesis via pharmacological intervention...
September 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28005280/abcg2-bcrp-specific-and-nonspecific-modulators
#19
REVIEW
Diana Peña-Solórzano, Simone Alexandra Stark, Burkhard König, Cesar Augusto Sierra, Cristian Ochoa-Puentes
Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2)...
September 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27957758/enzyme-tunnels-and-gates-as-relevant-targets-in-drug-design
#20
REVIEW
Sergio M Marques, Lukas Daniel, Tomas Buryska, Zbynek Prokop, Jan Brezovsky, Jiri Damborsky
Many enzymes contain tunnels and gates that are essential to their function. Gates reversibly switch between open and closed conformations and thereby control the traffic of small molecules-substrates, products, ions, and solvent molecules-into and out of the enzyme's structure via molecular tunnels. Many transient tunnels and gates undoubtedly remain to be identified, and their functional roles and utility as potential drug targets have received comparatively little attention. Here, we describe a set of general concepts relating to the structural properties, function, and classification of these interesting structural features...
September 2017: Medicinal Research Reviews
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