scholarly journals Recent Developments in Small-Molecule Ligands of Medicinal Relevance for Harnessing the Anticancer Potential of G-Quadruplexes

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 841
Author(s):  
Loukiani Savva ◽  
Savvas N. Georgiades
Keyword(s):  
Clinical Trials ◽  
Critical Discussion ◽  
Affinity Ligands ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Anticancer Effects ◽  
G Quadruplex ◽  
Small Molecule Ligands ◽  
Recent Developments ◽  
Further Development

G-quadruplexes, a family of tetraplex helical nucleic acid topologies, have emerged in recent years as novel targets, with untapped potential for anticancer research. Their potential stems from the fact that G-quadruplexes occur in functionally-important regions of the human genome, such as the telomere tandem sequences, several proto-oncogene promoters, other regulatory regions and sequences of DNA (e.g., rDNA), as well as in mRNAs encoding for proteins with roles in tumorigenesis. Modulation of G-quadruplexes, via interaction with high-affinity ligands, leads to their stabilization, with numerous observed anticancer effects. Despite the fact that only a few lead compounds for G-quadruplex modulation have progressed to clinical trials so far, recent advancements in the field now create conditions that foster further development of drug candidates. This review highlights biological processes through which G-quadruplexes can exert their anticancer effects and describes, via selected case studies, progress of the last few years on the development of efficient and drug-like G-quadruplex-targeted ligands, intended to harness the anticancer potential offered by G-quadruplexes. The review finally provides a critical discussion of perceived challenges and limitations that have previously hampered the progression of G-quadruplex-targeted lead compounds to clinical trials, concluding with an optimistic future outlook.

scholarly journals Marine Power on Cancer: Drugs, Lead Compounds, and Mechanisms

Marine Drugs ◽  
2021 ◽  
Vol 19 (9) ◽  
pp. 488
Author(s):  
Lichuan Wu ◽  
Ke Ye ◽  
Sheng Jiang ◽  
Guangbiao Zhou
Keyword(s):  
Mechanisms Of Action ◽  
Malignant Neoplasms ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Anticancer Effects ◽  
The Earth ◽  
Novel Drugs ◽  
Marine Compounds

Worldwide, 19.3 million new cancer cases and almost 10.0 million cancer deaths occur each year. Recently, much attention has been paid to the ocean, the largest biosphere of the earth that harbors a great many different organisms and natural products, to identify novel drugs and drug candidates to fight against malignant neoplasms. The marine compounds show potent anticancer activity in vitro and in vivo, and relatively few drugs have been approved by the U.S. Food and Drug Administration for the treatment of metastatic malignant lymphoma, breast cancer, or Hodgkin′s disease. This review provides a summary of the anticancer effects and mechanisms of action of selected marine compounds, including cytarabine, eribulin, marizomib, plitidepsin, trabectedin, zalypsis, adcetris, and OKI-179. The future development of anticancer marine drugs requires innovative biochemical biology approaches and introduction of novel therapeutic targets, as well as efficient isolation and synthesis of marine-derived natural compounds and derivatives.

scholarly journals Small Molecule Fluorescent Probes for G- Quadruplex Visualization as Potential Cancer Theranostic Agents

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 752 ◽  
Author(s):  
Pallavi Chilka ◽  
Nakshi Desai ◽  
Bhaskar Datta
Keyword(s):  
Small Molecule ◽  
Fluorescent Probes ◽  
Cancer Prognosis ◽  
Fluorescence Signal ◽  
Physiological Relevance ◽  
G Quadruplex ◽  
Small Molecule Ligands ◽  
Recent Developments ◽  
Theranostic Agents

G-quadruplexes have gained prominence over the past two decades for their role in gene regulation, control of anti-tumour activity and ageing. The physiological relevance and significance of these non-canonical structures in the context of cancer has been reviewed several times. Putative roles of G-quadruplexes in cancer prognosis and pathogenesis have spurred the search for small molecule ligands that are capable of binding and modulating the effect of such structures. On a related theme, small molecule fluorescent probes have emerged that are capable of selective recognition of G-quadruplex structures. These have opened up the possibility of direct visualization and tracking of such structures. In this review we outline recent developments on G-quadruplex specific small molecule fluorescent probes for visualizing G-quadruplexes. The molecules represent a variety of structural scaffolds, mechanism of quadruplex-recognition and fluorescence signal transduction. Quadruplex selectivity and in vivo imaging potential of these molecules places them uniquely as quadruplex-theranostic agents in the predominantly cancer therapeutic context of quadruplex-selective ligands.

scholarly journals Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2193
Author(s):  
Pedro Cruz-Vicente ◽  
Luís A. Passarinha ◽  
Samuel Silvestre ◽  
Eugenia Gallardo
Keyword(s):  
Clinical Trials ◽  
In Silico ◽  
Symptomatic Relief ◽  
Therapeutic Agents ◽  
Future Perspectives ◽  
Drug Candidates ◽  
Recent Developments ◽  
Progressive Neurodegeneration ◽  
Novel Drug ◽  
Parkinson Diseases

Neurodegenerative diseases (ND), including Alzheimer’s (AD) and Parkinson’s Disease (PD), are becoming increasingly more common and are recognized as a social problem in modern societies. These disorders are characterized by a progressive neurodegeneration and are considered one of the main causes of disability and mortality worldwide. Currently, there is no existing cure for AD nor PD and the clinically used drugs aim only at symptomatic relief, and are not capable of stopping neurodegeneration. Over the last years, several drug candidates reached clinical trials phases, but they were suspended, mainly because of the unsatisfactory pharmacological benefits. Recently, the number of compounds developed using in silico approaches has been increasing at a promising rate, mainly evaluating the affinity for several macromolecular targets and applying filters to exclude compounds with potentially unfavorable pharmacokinetics. Thus, in this review, an overview of the current therapeutics in use for these two ND, the main targets in drug development, and the primary studies published in the last five years that used in silico approaches to design novel drug candidates for AD and PD treatment will be presented. In addition, future perspectives for the treatment of these ND will also be briefly discussed.

Privileged Structures in the Design of Potential Drug Candidates for Neglected Diseases

2019 ◽  
Vol 26 (23) ◽  
pp. 4323-4354 ◽  
Author(s):  
Ana Cristina Lima Leite ◽  
José Wanderlan Pontes Espíndola ◽  
Marcos Veríssimo de Oliveira Cardoso ◽  
Gevanio Bezerra de Oliveira Filho
Keyword(s):  
Biologically Active ◽  
Neglected Diseases ◽  
Financial Return ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Wide Range ◽  
Methods Of Synthesis ◽  
Current Therapies ◽  
Resistant Strains ◽  
Privileged Structures

Background: Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. The current therapies to treat these diseases are based in drugs that lack of the desired effectiveness, affordable methods of synthesis and allow a way to emergence of resistant strains. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND). Methods: Based on the literature search from 2002 to 2016, we discuss how six privileged motifs, focusing phthalimide, isatin, indole, thiosemicarbazone, thiazole, and thiazolidinone are particularly recurrent in compounds active against some of neglected diseases. Results: It was observed that attention was paid particularly for Chagas disease, malaria, tuberculosis, schistosomiasis, leishmaniasis, dengue, African sleeping sickness (Human African Trypanosomiasis - HAT) and toxoplasmosis. It was possible to verify that, among the ND, antitrypanosomal and antiplasmodial activities were between the most searched. Besides, thiosemicarbazone moiety seems to be the most versatile and frequently explored scaffold. As well, phthalimide, isatin, thiazole, and thiazolidone nucleus have been also explored in the ND field. Conclusion: Some described compounds, appear to be promising drug candidates, while others could represent a valuable inspiration in the research for new lead compounds.

Current Approaches to Drug Discovery for Chagas Disease: Methodological Advances

2019 ◽  
Vol 22 (8) ◽  
pp. 509-520
Author(s):  
Cauê B. Scarim ◽  
Chung M. Chin
Keyword(s):  
Drug Discovery ◽  
Chagas Disease ◽  
Drug Candidates ◽  
Lead Compounds ◽  
New Drug ◽  
Compound Libraries ◽  
Screening Assays ◽  
Cruzi Infection

Background: In recent years, there has been an improvement in the in vitro and in vivo methodology for the screening of anti-chagasic compounds. Millions of compounds can now have their activity evaluated (in large compound libraries) by means of high throughput in vitro screening assays. Objective: Current approaches to drug discovery for Chagas disease. Method: This review article examines the contribution of these methodological advances in medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from the PubMed, Web of Science, and Scopus databases. Results: Here, we have shown that the promise is increasing each year for more lead compounds for the development of a new drug against Chagas disease. Conclusion: There is increased optimism among those working with the objective to find new drug candidates for optimal treatments against Chagas disease.

Recent Updates in the Alzheimer’s Disease Etiopathology and Possible Treatment Approaches: A Narrative Review of Current Clinical Trials

2020 ◽  
Vol 13 (4) ◽  
pp. 273-294 ◽  
Author(s):  
Elahe Zarini-Gakiye ◽  
Javad Amini ◽  
Nima Sanadgol ◽  
Gholamhassan Vaezi ◽  
Kazem Parivar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Small Molecules ◽  
Clinical Trial Design ◽  
Treatment Approaches ◽  
Drug Candidates ◽  
Novel Treatments ◽  
Approved Drugs ◽  
Tau Aggregation

Background: Alzheimer’s disease (AD) is the most frequent subtype of incurable neurodegenerative dementias and its etiopathology is still not clearly elucidated. Objective: Outline the ongoing clinical trials (CTs) in the field of AD, in order to find novel master regulators. Methods: We strictly reviewed all scientific reports from Clinicaltrials.gov and PubMed databases from January 2010 to January 2019. The search terms were “Alzheimer's disease” or “dementia” and “medicine” or “drug” or “treatment” and “clinical trials” and “interventions”. Manuscripts that met the objective of this study were included for further evaluations. Results: Drug candidates have been categorized into two main groups including antibodies, peptides or hormones (such as Ponezumab, Interferon β-1a, Solanezumab, Filgrastim, Levemir, Apidra, and Estrogen), and naturally-derived ingredients or small molecules (such as Paracetamol, Ginkgo, Escitalopram, Simvastatin, Cilostazo, and Ritalin-SR). The majority of natural candidates acted as anti-inflammatory or/and anti-oxidant and antibodies exert their actions via increasing amyloid-beta (Aβ) clearance or decreasing Tau aggregation. Among small molecules, most of them that are present in the last phases act as specific antagonists (Suvorexant, Idalopirdine, Intepirdine, Trazodone, Carvedilol, and Risperidone) or agonists (Dextromethorphan, Resveratrol, Brexpiprazole) and frequently ameliorate cognitive dysfunctions. Conclusion: The presences of a small number of candidates in the last phase suggest that a large number of candidates have had an undesirable side effect or were unable to pass essential eligibility for future phases. Among successful treatment approaches, clearance of Aβ, recovery of cognitive deficits, and control of acute neuroinflammation are widely chosen. It is predicted that some FDA-approved drugs, such as Paracetamol, Risperidone, Escitalopram, Simvastatin, Cilostazoand, and Ritalin-SR, could also be used in off-label ways for AD. This review improves our ability to recognize novel treatments for AD and suggests approaches for the clinical trial design for this devastating disease in the near future.

scholarly journals Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody–drug conjugates as lead drug candidates for clinical trials

2020 ◽  
Vol 12 ◽  
pp. 175883592092006
Author(s):  
Hang-Ping Yao ◽  
Sreedhar Reddy Suthe ◽  
Xiang-Min Tong ◽  
Ming-Hai Wang
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Targeted Therapeutics ◽  
Antibody Drug Conjugates ◽  
Drug Candidates ◽  
Drug Conjugates ◽  
Ron Receptor ◽  
Antibody Drug

The recepteur d’origine nantais (RON) receptor tyrosine kinase, belonging to the mesenchymal-to-epithelial transition proto-oncogene family, has been implicated in the pathogenesis of cancers derived from the colon, lung, breast, and pancreas. These findings lay the foundation for targeting RON for cancer treatment. However, development of RON-targeted therapeutics has not gained sufficient attention for the last decade. Although therapeutic monoclonal antibodies (TMABs) targeting RON have been validated in preclinical studies, results from clinical trials have met with limited success. This outcome diminishes pharmaceutical enthusiasm for further development of RON-targeted therapeutics. Recently, antibody–drug conjugates (ADCs) targeting RON have drawn special attention owing to their increased therapeutic activity. The rationale for developing anti-RON ADCs is based on the observation that cancer cells are not sufficiently addicted to RON signaling for survival. Thus, TMAB-mediated inhibition of RON signaling is ineffective for clinical application. In contrast, anti-RON ADCs combine a target-specific antibody with potent cytotoxins for cancer cell killing. This approach not only overcomes the shortcomings in TMAB-targeted therapies but also holds the promise for advancing anti-RON ADCs into clinical trials. In this review, we discuss the latest advancements in the development of anti-RON ADCs for targeted cancer therapy including drug conjugation profile, pharmacokinetic properties, cytotoxic effect in vitro, efficacy in tumor models, and toxicological activities in primates.

scholarly journals Medicinal Plants and Mushrooms with Immunomodulatory and Anticancer Properties—A Review on Hong Kong’s Experience

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2173
Author(s):  
Grace Gar-Lee Yue ◽  
Clara Bik-San Lau ◽  
Ping-Chung Leung
Keyword(s):  
Clinical Trials ◽  
Medicinal Plants ◽  
Infection Control ◽  
Immune Modulation ◽  
Evidence Based ◽  
Medicinal Mushroom ◽  
Immunomodulatory Effects ◽  
Anticancer Properties ◽  
Further Development ◽  
Insight Into

The immune modulating effects of selected herbs deserve careful studies to gain evidence-based support for their further development. We have been working hard on many items of medicinal herbs to gain insight into their immunomodulatory effects relevant to cancer treatment in particular, while infection control is not excluded. Nine of them have been selected to give the results of our exploration on their biological, particularly immunomodulatory activities. Since Hong Kong people especially favor one medicinal mushroom, viz. Coriolus versicolor, a number of clinical trials using Coriolus for cancer-related studies are included in this review. While immune modulation platforms are being built for relevant studies, a brief account on the research targets and related procedures are given.

scholarly journals Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 359
Author(s):  
Thai Thanh Hoang Thi ◽  
Estelle J. A. Suys ◽  
Jung Seok Lee ◽  
Dai Hai Nguyen ◽  
Ki Dong Park ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Physicochemical Properties ◽  
Solid Lipid Nanoparticles ◽  
Drug Delivery Systems ◽  
Lipid Nanoparticles ◽  
Therapeutic Vaccines ◽  
Cancer Nanomedicine ◽  
Fundamental Research ◽  
Further Development

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

scholarly journals Recent Developments of Antimony-Based Anodes for Sodium- and Potassium-Ion Batteries

2021 ◽  
Author(s):  
Bochao Chen ◽  
Ming Liang ◽  
Qingzhao Wu ◽  
Shan Zhu ◽  
Naiqin Zhao ◽  
...  
Keyword(s):  
Structural Characteristics ◽  
Low Cost ◽  
Potassium Ion ◽  
Research Progress ◽  
Research Directions ◽  
Weak Charge ◽  
Recent Developments ◽  
High Theoretical Capacity ◽  
Further Development ◽  
Sodium And Potassium

AbstractThe development of sodium-ion (SIBs) and potassium-ion batteries (PIBs) has increased rapidly because of the abundant resources and cost-effectiveness of Na and K. Antimony (Sb) plays an important role in SIBs and PIBs because of its high theoretical capacity, proper working voltage, and low cost. However, Sb-based anodes have the drawbacks of large volume changes and weak charge transfer during the charge and discharge processes, thus leading to poor cycling and rapid capacity decay. To address such drawbacks, many strategies and a variety of Sb-based materials have been developed in recent years. This review systematically introduces the recent research progress of a variety of Sb-based anodes for SIBs and PIBs from the perspective of composition selection, preparation technologies, structural characteristics, and energy storage behaviors. Moreover, corresponding examples are presented to illustrate the advantages or disadvantages of these anodes. Finally, we summarize the challenges of the development of Sb-based materials for Na/K-ion batteries and propose potential research directions for their further development.

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