scholarly journals Natural Cyclopeptides as Anticancer Agents in the Last 20 Years

2021 ◽  
Vol 22 (8) ◽  
pp. 3973
Author(s):  
Jia-Nan Zhang ◽  
Yi-Xuan Xia ◽  
Hong-Jie Zhang
Keyword(s):  
Anticancer Agents ◽  
Cyclic Peptides ◽  
Structural Features ◽  
Pharmaceutical Companies ◽  
Chemical Structures ◽  
The Past ◽  
Structural Rigidity ◽  
Structure Activity ◽  
Academic Researchers ◽  
Terminal Amino

Cyclopeptides or cyclic peptides are polypeptides formed by ring closing of terminal amino acids. A large number of natural cyclopeptides have been reported to be highly effective against different cancer cells, some of which are renowned for their clinical uses. Compared to linear peptides, cyclopeptides have absolute advantages of structural rigidity, biochemical stability, binding affinity as well as membrane permeability, which contribute greatly to their anticancer potency. Therefore, the discovery and development of natural cyclopeptides as anticancer agents remains attractive to academic researchers and pharmaceutical companies. Herein, we provide an overview of anticancer cyclopeptides that were discovered in the past 20 years. The present review mainly focuses on the anticancer efficacies, mechanisms of action and chemical structures of cyclopeptides with natural origins. Additionally, studies of the structure–activity relationship, total synthetic strategies as well as bioactivities of natural cyclopeptides are also included in this article. In conclusion, due to their characteristic structural features, natural cyclopeptides have great potential to be developed as anticancer agents. Indeed, they can also serve as excellent scaffolds for the synthesis of novel derivatives for combating cancerous pathologies.

Carboxylesterase Inhibitors: An Update

2018 ◽  
Vol 25 (14) ◽  
pp. 1627-1649 ◽  
Author(s):  
Li-Wei Zou ◽  
Qiang Jin ◽  
Dan-Dan Wang ◽  
Qing-Kai Qian ◽  
Da-Cheng Hao ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biomedical Applications ◽  
Metabolic Activation ◽  
Structural Features ◽  
Inhibition Mechanism ◽  
The Past ◽  
Structure Activity ◽  
Potential Applications ◽  
Hydrolysis Of

Mammalian carboxylesterases are key serine hydrolases that catalyze the hydrolysis of a wide variety of ester compounds in the corresponding carboxylic acids and alcohols. In human, two major carboxylesterases, CES1 and CES2, have been identified and well-studied over the past decade. CES1 inhibitors have potential applications in the treatment of hypertriglyceridaemia, obesity and type 2 diabetes, owing to that this enzyme plays prominent role in the metabolism of cholesteryl esters. CES2 plays crucial roles in the metabolic activation of many prodrugs including anticancer agents capecitabine and CPT-11. Co-administration with CES2 inhibitors may ameliorate CPT-11 associated lifethreatening diarrhea or improve the half-lives of CES2-substrate drugs. The important roles of carboxylesterases in both endogenous and xenobiotic metabolism arouse great interest in the discovery and development of potent and selective inhibitors against these enzymes. This review is focused on the application potentials and recent advances in the discovery and development of carboxylesterases inhibitors. The inhibitory capacities and inhibition mechanism of a variety of carboxylesterases inhibitors including synthetic, semi-synthetic and natural compounds are comprehensively summarized. Furthermore, the key structural features and structure-activity relationships (SARs) of different classes of CES1 and CES2 inhibitors are discussed. All information and knowledge summarized in this review will be very helpful for the medicinal chemists to design and develop more potent and highly selective carboxylesterases inhibitors for potential biomedical applications.

scholarly journals Sphingolipids of Asteroidea and Holothuroidea: Structures and Biological Activities

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 330
Author(s):  
Timofey V. Malyarenko ◽  
Alla A. Kicha ◽  
Valentin A. Stonik ◽  
Natalia V. Ivanchina
Keyword(s):  
Marine Invertebrates ◽  
Biological Activities ◽  
Complete Information ◽  
Structural Features ◽  
Marine Organisms ◽  
Structural Components ◽  
Chemical Structures ◽  
The Past ◽  
Complex Lipids ◽  
Complex Sphingolipids

Sphingolipids are complex lipids widespread in nature as structural components of biomembranes. Commonly, the sphingolipids of marine organisms differ from those of terrestrial animals and plants. The gangliosides are the most complex sphingolipids characteristic of vertebrates that have been found in only the Echinodermata (echinoderms) phylum of invertebrates. Sphingolipids of the representatives of the Asteroidea and Holothuroidea classes are the most studied among all echinoderms. In this review, we have summarized the data on sphingolipids of these two classes of marine invertebrates over the past two decades. Recently established structures, properties, and peculiarities of biogenesis of ceramides, cerebrosides, and gangliosides from starfishes and holothurians are discussed. The purpose of this review is to provide the most complete information on the chemical structures, structural features, and biological activities of sphingolipids of the Asteroidea and Holothuroidea classes.

scholarly journals Brown Seaweed Defensive Chemicals: A Structure-activity Relationship Approach for the Marine Environment

2009 ◽  
Vol 4 (2) ◽  
pp. 1934578X0900400 ◽  
Author(s):  
Éverson Miguel Bianco ◽  
Valéria Laneuville Teixeira ◽  
Renato Crespo Pereira ◽  
Alessandra Mendonça Teles de Souza ◽  
Pedro Nucci ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Pathogenic Bacteria ◽  
Brown Seaweed ◽  
Structure Activity Relationship ◽  
Structural Features ◽  
Activity Relationship ◽  
Chemical Structures ◽  
Structure Activity ◽  
Minimum Requirements ◽  
New Perspective

The literature describes several diterpenes from brown seaweeds that act as defensive chemicals against natural enemies, such as competitors, epiphytes, pathogenic bacteria and herbivores. A structure-activity relationship is here presented using a new molecular modeling approach to identify structural and chemical features important to the defensive profile of four structurally related diterpenes (three dolastanes and one seco-dolastane) from Canistrocarpus cervicornis against the feeding process of the omnivorous sea urchin Lytechinus variegatus. Our experimental data revealed the herbivory inhibitory profile (HIE) for three of these evaluated compounds with (4R, 7R, 14S)-4α, 7α-diacetoxy-14-hydroxydolast-1(15),8-diene presenting the highest effect (HIE = 70%). Interestingly, the molecular modeling results infer that this biological activity seems to be related to several different structural features, including HOMO distribution, the molecular structure conformation, and the fulfillment of minimum requirements regarding molecular weight. These results reinforce the hypothesis about the intricate biological mechanism of these molecules due to the complexity of their chemical structures. Our work may help in the understanding of these defensive mechanisms and point to a new perspective of ecological and/or evolutionary evaluation in this area.

Discovery and development of macrolides as anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Rongli Liu ◽  
Yani Hou ◽  
Yijun Gu
Keyword(s):  
Anticancer Agents ◽  
Rational Design ◽  
Chemotherapeutic Agents ◽  
Lifestyle Changes ◽  
Therapeutic Interventions ◽  
The Past ◽  
Development Of Resistance ◽  
Structure Activity ◽  
Activity Structure ◽  
Life Threatening

: Cancer is a life-threatening destructive disease. In the past several decades, the incidence of cancer has been dramatically increased mostly due to lifestyle changes. Chemotherapy plays an important role in the treatment of cancer, but the development of resistance against chemotherapeutic agents, the side effects, and non-specific toxicity threatens the efficiency of anticancer agents. Accordingly, it is necessary to develop novel anticancer drugs. Beyond the classical antibacterial activity, macrolides also demonstrated potential effects against both drug-sensitive and drug-resistant cancers through modulating diverse targets and signaling pathways, so rational design of macrolides may generate valuable therapeutic interventions for the treatment of cancers. The purpose of the present review article is to outline the current developments in macrolides with an emphasis on anticancer activity, structure-activity relationships, and mechanisms of action to lay the path for the development of novel macrolide anticancer candidates.

scholarly journals Structure-Activity Relationships of Benzothiazole-Based Hsp90 C-Terminal-Domain Inhibitors

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1283
Author(s):  
Jaka Dernovšek ◽  
Živa Zajec ◽  
Martina Durcik ◽  
Lucija Peterlin Mašič ◽  
Martina Gobec ◽  
...  
Keyword(s):  
Heat Shock ◽  
Anticancer Agents ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Binding Mode ◽  
Structural Features ◽  
Dynamics Simulation ◽  
Terminal Domain ◽  
Structure Activity ◽  
Shock Response

Heat shock protein 90 (Hsp90) is a chaperone responsible for the maturation of many cancer-related proteins, and is therefore an important target for the design of new anticancer agents. Several Hsp90 N-terminal domain inhibitors have been evaluated in clinical trials, but none have been approved as cancer therapies. This is partly due to induction of the heat shock response, which can be avoided using Hsp90 C-terminal-domain (CTD) inhibition. Several structural features have been shown to be useful in the design of Hsp90 CTD inhibitors, including an aromatic ring, a cationic center and the benzothiazole moiety. This study established a previously unknown link between these structural motifs. Using ligand-based design methodologies and structure-based pharmacophore models, a library of 29 benzothiazole-based Hsp90 CTD inhibitors was prepared, and their antiproliferative activities were evaluated in MCF-7 breast cancer cells. Several showed low-micromolar IC50, with the most potent being compounds 5g and 9i (IC50, 2.8 ± 0.1, 3.9 ± 0.1 μM, respectively). Based on these results, a ligand-based structure–activity relationship model was built, and molecular dynamics simulation was performed to elaborate the binding mode of compound 9i. Moreover, compound 9i showed degradation of Hsp90 client proteins and no induction of the heat shock response.

Autophagy-regulating N-heterocycles derivatives as potential anticancer agents

2020 ◽  
Vol 12 (3) ◽  
pp. 223-242 ◽  
Author(s):  
Xiaoxia Liang ◽  
Li Zhang ◽  
Fanglong Li ◽  
Shangxian Luan ◽  
Changliang He ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Structural Features ◽  
New Drugs ◽  
Therapeutic Effects ◽  
Antitumor Activities ◽  
Antitumor Therapy ◽  
Drug Candidates ◽  
The Past ◽  
First Time

As a double-edged sword, autophagy in cancer cells could either suppress or promote tumorigenesis. Nowadays, more and more natural compounds with autophagy-regulating activities exhibit therapeutic effects against various cancers. N-Heterocycle derivatives plays an important role for discovery new drugs. In this review, we summarize and classify 116 N-heterocycle derivatives with autophagy-regulating activities in the past decade into 12 classes according to structure characteristics. The structural features, bioactivities, mechanism and problems faced in this field are discussed and reported for the first time. Some of these even exhibited outstanding in vivo antitumor activities, including bisaminoquinoline (3), pancratistatin (8), 10-hydroxyevodiamine (18), lycorine (28), piperine (31) and iridium (III) complex (57), which are potential drug candidates for antitumor therapy.

scholarly journals Natural Polypropionates in 1999–2020: An Overview of Chemical and Biological Diversity

Marine Drugs ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. 569
Author(s):  
Zhaoming Liu ◽  
Hongxin Liu ◽  
Weimin Zhang
Keyword(s):  
Biological Diversity ◽  
Biological Activities ◽  
Structural Features ◽  
Chemical Diversity ◽  
Research Papers ◽  
Chemical Structures ◽  
The Past ◽  
Current Review ◽  
Large Subgroup ◽  
The Relationship

Natural polypropionates (PPs) are a large subgroup of polyketides with diverse structural features and bioactivities. Most of the PPs are discovered from marine organisms including mollusks, fungi and actinomycetes, while some of them are also isolated from terrestrial resources. An increasing number of studies about PPs have been carried out in the past two decades and an updated review is needed. In this current review, we summarize the chemical structures and biological activities of 164 natural PPs reported in 67 research papers from 1999 to 2020. The isolation, structural features and bioactivities of these PPs are discussed in detail. The chemical diversity, bioactive diversity, biodiversity and the relationship between chemical classes and the bioactivities are also concluded.

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 118-119
Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun
Keyword(s):  
Electron Microscopy ◽  
Structural Organization ◽  
Cell Types ◽  
Structural Features ◽  
Molecular Architecture ◽  
The Past ◽  
Keratin Filaments ◽  
Different Types ◽  
10 Nm Filaments ◽  
Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

HAZARD: An Expert System for Risk Assessment of Environmental Chemicals

1987 ◽  
Vol 26 (01) ◽  
pp. 13-23 ◽  
Author(s):  
H. W. Gottinger
Keyword(s):  
Expert System ◽  
Structural Information ◽  
Chemical Carcinogenesis ◽  
Structural Features ◽  
Environmental Chemicals ◽  
Chemical Carcinogens ◽  
Carcinogenic Activity ◽  
Current State ◽  
Structure Activity ◽  
Carcinogenic Potential

AbstractThe purpose of this paper is to report on an expert system in design that screens for potential hazards from environmental chemicals on the basis of structure-activity relationships in the study of chemical carcinogenesis, particularly with respect to analyzing the current state of known structural information about chemical carcinogens and predicting the possible carcinogenicity of untested chemicals. The structure-activity tree serves as an index of known chemical structure features associated with carcinogenic activity. The basic units of the tree are the principal recognized classes of chemical carcinogens that are subdivided into subclasses known as nodes according to specific structural features that may reflect differences in carcinogenic potential among chemicals in the class. An analysis of a computerized data base of known carcinogens (knowledge base) is proposed using the structure-activity tree in order to test the validity of the tree as a classification scheme (inference engine).

Policy Making Introduction

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Nina TERREY ◽  
Sabine JUNGINGER
Keyword(s):  
Policy Implementation ◽  
Policy Making ◽  
Creative Industries ◽  
Design Management ◽  
Support Design ◽  
The Past ◽  
Academic Researchers ◽  
Design Activities ◽  
The Relationship ◽  
Professional Impact

The relationship that exists between design, policies and governance is quite complex and presents academic researchers continuously with new opportunities to engage and explore aspects relevant to design management. Over the past years, we have witnessed how the earlier focus on developing policies for design has shifted to an interest in understanding the ways in which design contributes to policy-making and policy implementation. Research into policies for design has produced insights into how policy-making decisions can advance professional impact and opportunities for designers and the creative industries. This research looked into how design researchers and design practitioners themselves can benefit from specific policies that support design activities and create the space for emerging design processes.

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