scholarly journals In Silico Design and Selection of New Tetrahydroisoquinoline-Based CD44 Antagonist Candidates

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1877
Author(s):  
Angel J. Ruiz-Moreno ◽  
Atilio Reyes-Romero ◽  
Alexander Dömling ◽  
Marco A. Velasco-Velázquez
Keyword(s):  
Md Simulations ◽  
Binding Mode ◽  
Cancer Therapies ◽  
Cd44 Isoforms ◽  
Computational Docking ◽  
Explicit Solvent ◽  
Anti Cancer ◽  
Different Types ◽  
Target Binding ◽  
Selection Of

CD44 promotes metastasis, chemoresistance, and stemness in different types of cancer and is a target for the development of new anti-cancer therapies. All CD44 isoforms share a common N-terminal domain that binds to hyaluronic acid (HA). Herein, we used a computational approach to design new potential CD44 antagonists and evaluate their target-binding ability. By analyzing 30 crystal structures of the HA-binding domain (CD44HAbd), we characterized a subdomain that binds to 1,2,3,4-tetrahydroisoquinoline (THQ)-containing compounds and is adjacent to residues essential for HA interaction. By computational combinatorial chemistry (CCC), we designed 168,190 molecules and compared their conformers to a pharmacophore containing the key features of the crystallographic THQ binding mode. Approximately 0.01% of the compounds matched the pharmacophore and were analyzed by computational docking and molecular dynamics (MD). We identified two compounds, Can125 and Can159, that bound to human CD44HAbd (hCD44HAbd) in explicit-solvent MD simulations and therefore may elicit CD44 blockage. These compounds can be easily synthesized by multicomponent reactions for activity testing and their binding mode, reported here, could be helpful in the design of more potent CD44 antagonists.

scholarly journals N-cadherin antagonists as oncology therapeutics

2015 ◽  
Vol 370 (1661) ◽  
pp. 20140039 ◽  
Author(s):  
Orest W. Blaschuk
Keyword(s):  
Cell Adhesion ◽  
Cancer Progression ◽  
Structural Integrity ◽  
Cancer Therapies ◽  
Transmembrane Glycoprotein ◽  
Anti Cancer ◽  
Different Types ◽  
Poorly Differentiated ◽  
Novel Strategy

The cell adhesion molecule (CAM), N-cadherin, has emerged as an important oncology therapeutic target. N-cadherin is a transmembrane glycoprotein mediating the formation and structural integrity of blood vessels. Its expression has also been documented in numerous types of poorly differentiated tumours. This CAM is involved in regulating the proliferation, survival, invasiveness and metastasis of cancer cells. Disruption of N-cadherin homophilic intercellular interactions using peptide or small molecule antagonists is a promising novel strategy for anti-cancer therapies. This review discusses: the discovery of N-cadherin, the mechanism by which N-cadherin promotes cell adhesion, the role of N-cadherin in blood vessel formation and maintenance, participation of N-cadherin in cancer progression, the different types of N-cadherin antagonists and the use of N-cadherin antagonists as anti-cancer drugs.

scholarly journals MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 29 ◽  
Author(s):  
Hyun Ah Seo ◽  
Sokviseth Moeng ◽  
Seokmin Sim ◽  
Hyo Jeong Kuh ◽  
Soo Young Choi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Different Types ◽  
Therapeutic Responses

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

scholarly journals Solvent effects on the properties of hyperbranched polythiophenes

2016 ◽  
Vol 18 (35) ◽  
pp. 24610-24619
Author(s):  
Juan Torras ◽  
David Zanuy ◽  
David Aradilla ◽  
Carlos Alemán
Keyword(s):  
Solvent Effects ◽  
Md Simulations ◽  
Conformational Flexibility ◽  
Explicit Solvent ◽  
Different Types ◽  
Solvent Molecules

QM/MM-MD simulations of dendrimers using explicit solvent molecules capture the conformational flexibility and microfluctuations induced by different types of solvents.

scholarly journals Extensive Evaluation of Force Fields for G-Quadruplexes

2021 ◽  
Author(s):  
Na Li ◽  
Tong Zhu
Keyword(s):  
Force Field ◽  
Md Simulation ◽  
Comprehensive Evaluation ◽  
Force Fields ◽  
Md Simulations ◽  
Extensive Evaluation ◽  
Explicit Solvent ◽  
Quantum Chemistry Calculations ◽  
Anti Cancer ◽  
Sticking Point

<p><a></a><a></a><a>G-Quadruplexes</a> (GQs), folded by guanine-rich <a></a><a></a><a>nucleic acid</a> <a></a><a></a><a></a><a>sequences</a>, involve in gene expression processes and closely associated with the formation of tumors. So far, GQ has drawn widespread attention for its notable application of serving as potential anti-cancer target. Recently, theoretical studies for GQs have achieved significant progress, most of which are inseparable from molecular dynamics (MD) simulation. As a necessary tool to explore <a></a><a></a><a>dynamics behavior</a> of molecules, MD simulations strictly depend on force field parameters, which is a sticking point to obtain accurate results. Currently, many force fields for nucleic acids have been developed, but none of them have been accepted widely for GQs. In this paper, we selected five popular force fields, which are parmbsc0, parmbsc1, OL15, Drude2017 and AMOEBANUC17, and conducted explicit-solvent MD simulations on two DNA GQs respectively. We evaluated these force fields from many aspects in detail. Meanwhile, we compared conformational energy using quantum chemistry calculations. With the comprehensive evaluation, Drude2017 achieved better description for GQs, which we suggest that using Drude2017 force field should <a></a><a></a><a>be taken into account</a> first when investigating GQs by MD simulation<a></a><a></a><a></a><a></a><a>.</a></p>

scholarly journals An Emerging Approach for Combination Therapy of Cancer: The Role of Immunogenic Cell Death

2020 ◽  
Author(s):  
Zahra Asadzadeh ◽  
Elham Safarzadeh ◽  
Sahar Safaei ◽  
Ali Baradaran ◽  
Ali Mohammadi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Immune Escape ◽  
Immunogenic Cell Death ◽  
Cancer Therapies ◽  
Tumor Immune Escape ◽  
Anti Cancer ◽  
Different Types ◽  
Molecular Patterns

Cell death resistance is a key feature of tumor cells. One of the main anti-cancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells.

scholarly journals Extensive Evaluation of Force Fields for G-Quadruplexes

2021 ◽  
Author(s):  
Na Li ◽  
Tong Zhu
Keyword(s):  
Force Field ◽  
Md Simulation ◽  
Comprehensive Evaluation ◽  
Force Fields ◽  
Md Simulations ◽  
Extensive Evaluation ◽  
Explicit Solvent ◽  
Quantum Chemistry Calculations ◽  
Anti Cancer ◽  
Sticking Point

<p><a></a><a></a><a>G-Quadruplexes</a> (GQs), folded by guanine-rich <a></a><a></a><a>nucleic acid</a> <a></a><a></a><a></a><a>sequences</a>, involve in gene expression processes and closely associated with the formation of tumors. So far, GQ has drawn widespread attention for its notable application of serving as potential anti-cancer target. Recently, theoretical studies for GQs have achieved significant progress, most of which are inseparable from molecular dynamics (MD) simulation. As a necessary tool to explore <a></a><a></a><a>dynamics behavior</a> of molecules, MD simulations strictly depend on force field parameters, which is a sticking point to obtain accurate results. Currently, many force fields for nucleic acids have been developed, but none of them have been accepted widely for GQs. In this paper, we selected five popular force fields, which are parmbsc0, parmbsc1, OL15, Drude2017 and AMOEBANUC17, and conducted explicit-solvent MD simulations on two DNA GQs respectively. We evaluated these force fields from many aspects in detail. Meanwhile, we compared conformational energy using quantum chemistry calculations. With the comprehensive evaluation, Drude2017 achieved better description for GQs, which we suggest that using Drude2017 force field should <a></a><a></a><a>be taken into account</a> first when investigating GQs by MD simulation<a></a><a></a><a></a><a></a><a>.</a></p>

ANTICANCER EFFECT OF UVARIA GENUS

2014 ◽  
pp. 98-101
Author(s):  
Thi Bich Hien Le ◽  
Viet Duc Ho ◽  
Thi Hoai Nguyen
Keyword(s):  
Biological Activities ◽  
Current Trend ◽  
Healthcare Systems ◽  
Chemical Compositions ◽  
Cancer Therapies ◽  
Pharmacological Effects ◽  
Anticancer Effect ◽  
Anti Cancer ◽  
Tropical Areas ◽  
Cancer Activity

Nowadays, cancer treatment has been a big challenge to healthcare systems. Most of clinical anti-cancer therapies are toxic and cause adverse effects to human body. Therefore, current trend in science is seeking and screening of natural compounds which possess antineoplastic activities to utilize in treatment. Uvaria L. - Annonaceae includes approximately 175 species spreading over tropical areas of Asia, Australia, Africa and America. Studies on chemical compositions and pharmacological effects of Uvaria showed that several compound classes in this genus such as alkaloid, flavonoid, cyclohexen derivaties, acetogenin, steroid, terpenoid, etc. indicate considerable biological activities, for example anti-tumor, anti-cancer, antibacterial, antifungal, antioxidant, etc. Specifically, anti-cancer activity of fractions of extract and pure isolated compounds stands out for cytotoxicity against many cancer cell lines. This study provides an overview of anti-cancer activity of Uvaria and suggests a potential for further studies on seeking and developing novel anti-cancer compounds. Key words: Anti-cancer, Uvaria.

Anticancer Properties of Essential Oils: An Overview

2018 ◽  
Vol 18 (10) ◽  
pp. 957-966 ◽  
Author(s):  
Milene Aparecida Andrade ◽  
Mariana Aparecida Braga ◽  
Pedro Henrique Souza Cesar ◽  
Marcus Vinicius Cardoso Trento ◽  
Mariana Araújo Espósito ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Essential Oils ◽  
Public Health Problem ◽  
Mechanisms Of Action ◽  
Low Molecular Weight ◽  
Anticancer Properties ◽  
Anti Cancer ◽  
Different Types ◽  
Antitumor Properties ◽  
Pharmaceutical Properties

Background: Essential oils are complex mixtures of low molecular weight compounds extracted from plants. Their main constituents are terpenes and phenylpropanoids, which are responsible for their biological and pharmaceutical properties, such as insecticidal, parasiticidal, antimicrobial, antioxidant, anti-inflammatory, analgesic, antinociceptive, anticarcinogenic, and antitumor properties. Cancer is a complex genetic disease considered as a serious public health problem worldwide, accounting for more than 8 million deaths annually. Objective: The activities of prevention and treatment of different types of cancer and the medicinal potential of essential oils are addressed in this review. Conclusion: Several studies have demonstrated anti-carcinogenic and antitumor activity for many essential oils obtained from various plant species. They may be used as a substitution to or in addition to conventional anti-cancer therapy. Although many studies report possible mechanisms of action for essential oils compounds, more studies are necessary in order to apply them safely and appropriately in cancer therapy.

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