scholarly journals Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids

2021 ◽  
Vol 12 ◽  
Author(s):  
Mounir Tilaoui ◽  
Hassan Ait Mouse ◽  
Abdelmajid Zyad
Keyword(s):  
Anticancer Drugs ◽  
Primary Source ◽  
Cancer Drug ◽  
Multifactorial Disease ◽  
Preclinical Research ◽  
Drug Candidates ◽  
Tumor Relapse ◽  
The Past ◽  
Molecular Mechanism Of Action ◽  
Physiological And Biochemical

Cancer is a complex multifactorial disease that results from alterations in many physiological and biochemical functions. Over the last few decades, it has become clear that cancer cells can acquire multidrug resistance to conventional anticancer drugs, resulting in tumor relapse. Thus, there is a continuous need to discover new and effective anticancer drugs. Natural products from plants have served as a primary source of cancer drugs and continue to provide new plant-derived anticancer drugs. The present review describes plant-based alkaloids, which have been reported as active or potentially active in cancer treatment within the past 4 years (2017–2020), both in preclinical research and/or in clinical trials. In addition, recent insights into the possible molecular mechanism of action of alkaloid prodrugs naturally present in plants are also highlighted.

scholarly journals Special Issue “Anticancer Drugs”

2019 ◽  
Vol 12 (3) ◽  
pp. 134 ◽  
Author(s):  
Mary J. Meegan ◽  
Niamh M. O’Boyle
Keyword(s):  
Biological Activity ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Special Issue ◽  
Preclinical Research ◽  
Design Synthesis ◽  
Drug Conjugates ◽  
Molecular Mechanism Of Action ◽  
The Relationship ◽  
Selection Of

The focus of this Special Issue of Pharmaceuticals is on the design, synthesis, and molecular mechanism of action of novel antitumor, drugs with a special emphasis on the relationship between the chemical structure and the biological activity of the molecules. This Special Issue also provides an understanding of the biologic and genotypic context in which targets are selected for oncology drug discovery, thus providing a rationalization for the biological activity of these drugs and guiding the design of more effective agents. In this Special Issue of Pharmaceuticals dedicated to anticancer drugs, we present a selection of preclinical research papers including both traditional chemotherapeutic agents and newer more targeted therapies and biological agents. We have included articles that report the design of small molecules with promising anticancer activity as tubulin inhibitors, vascular targeting agents, and topoisomerase targeting agents, alongside a comprehensive review of clinically successful antibody-drug conjugates used in cancer treatment.

Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics

2018 ◽  
Vol 25 (5) ◽  
pp. 636-658 ◽  
Author(s):  
Jan Pokorny ◽  
Lucie Borkova ◽  
Milan Urban
Keyword(s):  
Biological Activities ◽  
Synthetic Approach ◽  
Clinical Use ◽  
New Approach ◽  
Click Reactions ◽  
Drug Candidates ◽  
The Past ◽  
Low Toxicity ◽  
New Compounds ◽  
Potential Therapeutics

Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates.

Molecular Topological Properties of Alkylating Agents Based Anticancer Drug Candidates Via Some Ve-degree Topological Indices

2020 ◽  
Vol 16 (2) ◽  
pp. 190-195 ◽  
Author(s):  
Süleyman Ediz ◽  
Murat Cancan
Keyword(s):  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Alkylating Agents ◽  
Topological Indices ◽  
Pharmacological Properties ◽  
Topological Properties ◽  
Drug Candidates ◽  
New Drug ◽  
Atom Bond ◽  
Dual Target

Background: Reckoning molecular topological indices of drug structures gives the data about the underlying topology of these drug structures. Novel anticancer drugs have been leading by researchers to produce ideal drugs. Materials and Methods: Pharmacological properties of these new drug agents explored by utilizing simulation strategies. Topological indices additionally have been utilized to research pharmacological properties of some drug structures. Novel alkylating agents based anticancer drug candidates and ve-degree molecular topological indices have been introduced recently. Results and Conclusion: In this study we calculate ve-degree atom-bond connectivity, harmonic, geometric-arithmetic and sum-connectivity molecular topological indices for the newly defined alkylating agents based dual-target anticancer drug candidates.

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

scholarly journals Nexus between COVID-19 and periodontal disease

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052110026
Author(s):  
Kanchana Sukumar ◽  
Anupama Tadepalli
Keyword(s):  
Periodontal Disease ◽  
Host Cells ◽  
Multifactorial Disease ◽  
Tissue Destruction ◽  
The Past ◽  
Appropriate Care ◽  
Bacterial Stimulation ◽  
Plaque Control ◽  
Disease Understanding ◽  
Pro Inflammatory Cytokines

Over the past several decades, studies have demonstrated the existence of bi-directional relationships between periodontal disease and systemic conditions. Periodontitis is a polymicrobial and multifactorial disease involving both host and environmental factors. Tissue destruction is primarily associated with hyperresponsiveness of the host resulting in release of inflammatory mediators. Pro-inflammatory cytokines play a major role in bacterial stimulation and tissue destruction. In addition, these cytokines are thought to underlie the associations between periodontitis and systemic conditions. Current research suggests that increased release of cytokines from host cells, referred to as the cytokine storm, is associated with disease progression in patients with coronavirus disease 2019 (COVID-19). An intersection between periodontitis and pulmonary disease is biologically plausible. Hence, we reviewed the evidence linking COVID-19, cytokines, and periodontal disease. Plaque control is essential to prevent exchange of bacteria between the mouth and the lungs, reducing the risk of lung disease. Understanding these associations may help identify individuals at high risk and deliver appropriate care at early stages.

scholarly journals Modern Synthetic Methods for the Stereoselective Construction of 1,3-Dienes

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 249
Author(s):  
Raquel G. Soengas ◽  
Humberto Rodríguez-Solla
Keyword(s):  
Organic Chemistry ◽  
Natural Products ◽  
Functional Group ◽  
Biological Activities ◽  
Synthetic Methods ◽  
Bond Forming ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

The 1,3-butadiene motif is widely found in many natural products and drug candidates with relevant biological activities. Moreover, dienes are important targets for synthetic chemists, due to their ability to give access to a wide range of functional group transformations, including a broad range of C-C bond-forming processes. Therefore, the stereoselective preparation of dienes have attracted much attention over the past decades, and the search for new synthetic protocols continues unabated. The aim of this review is to give an overview of the diverse methodologies that have emerged in the last decade, with a focus on the synthetic processes that meet the requirements of efficiency and sustainability of modern organic chemistry.

scholarly journals NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuan Wang ◽  
Jun Cai ◽  
Lei Zhao ◽  
Dejun Zhang ◽  
Guojie Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Bioinformatics Analysis ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Self Renewal ◽  
Tumor Relapse ◽  
The Past ◽  
Overwhelming Evidence ◽  
Novel Therapeutic Strategies

AbstractExperimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent studies have also implicated NUMB as a PCa suppressor and an inhibitor of PCa stem cells (PCSCs); however, exactly how NUMB functions in these contexts remains unclear. Here, by employing bioinformatics analysis and luciferase assays and by conducting rescue experiments, we first show that NUMB is directly targeted by microRNA-9-5p (miR-9-5p), an oncogenic miR associated with poor prognosis in many malignancies. We further show that miR-9-5p levels are inversely correlated with NUMB expression in CD44+ PCSCs. miR-9-5p reduced NUMB expression and inhibited numerous PCSC properties including proliferation, migration, invasion as well as self-renewal. Strikingly, overexpression of NUMB in CD44+ PCSCs overcame all of the above PCSC properties enforced by miR-9-5p. Taken together, our results suggest that inhibiting the expression of the oncomiR miR-9-5p and overexpressing NUMB may represent novel therapeutic strategies to target PCSCs and PCa metastasis.

scholarly journals Bioactive Secondary Metabolites of the Genus Diaporthe and Anamorph Phomopsis from Terrestrial and Marine Habitats and Endophytes: 2010–2019

2021 ◽  
Vol 9 (2) ◽  
pp. 217
Author(s):  
Tang-Chang Xu ◽  
Yi-Han Lu ◽  
Jun-Fei Wang ◽  
Zhi-Qiang Song ◽  
Ya-Ge Hou ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Small Molecules ◽  
Host Plants ◽  
Plant Pathogens ◽  
Bioactive Metabolites ◽  
Drug Candidates ◽  
The Past ◽  
Marine Habitats ◽  
Bioactive Secondary Metabolites ◽  
Unidentified Species

The genus Diaporthe and its anamorph Phomopsis are distributed worldwide in many ecosystems. They are regarded as potential sources for producing diverse bioactive metabolites. Most species are attributed to plant pathogens, non-pathogenic endophytes, or saprobes in terrestrial host plants. They colonize in the early parasitic tissue of plants, provide a variety of nutrients in the cycle of parasitism and saprophytism, and participate in the basic metabolic process of plants. In the past ten years, many studies have been focused on the discovery of new species and biological secondary metabolites from this genus. In this review, we summarize a total of 335 bioactive secondary metabolites isolated from 26 known species and various unidentified species of Diaporthe and Phomopsis during 2010–2019. Overall, there are 106 bioactive compounds derived from Diaporthe and 246 from Phomopsis, while 17 compounds are found in both of them. They are classified into polyketides, terpenoids, steroids, macrolides, ten-membered lactones, alkaloids, flavonoids, and fatty acids. Polyketides constitute the main chemical population, accounting for 64%. Meanwhile, their bioactivities mainly involve cytotoxic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, anti-algae, phytotoxic, and enzyme inhibitory activities. Diaporthe and Phomopsis exhibit their potent talents in the discovery of small molecules for drug candidates.

Structural activity relationship of metallo-aminoquines as a next generation antimalarials

2022 ◽  
Vol 22 ◽  
Author(s):  
Mohammad Abid ◽  
Shailja Singh ◽  
Timothy J. Egan ◽  
Mukesh C. Joshi
Keyword(s):  
Plasmodium Species ◽  
Toxic Metal ◽  
Multi Drug Resistance ◽  
Drug Candidates ◽  
Malaria Therapy ◽  
The Past ◽  
Common Infectious Disease ◽  
Structural Activity Relationship ◽  
Relationship Of ◽  
Children Under 5

Apicomplexian parasite of the genus Plasmodium is the causative agent of malaria, one of the most devastating, furious and common infectious disease throughout the world. According to the latest World malaria report, there were 229 million cases of malaria in 2019 majorly consisting of children under 5 years of age. Some of known analogues viz. quinine, quinoline-containing compounds have been used for last century in the clinical treatment of malaria. Past few decades have witnessed the emergence of multi-drug resistance (MDR) strains of Plasmodium species to existing antimalarials pressing the need for new drug candidates. For the past few decades bioorganometallic approach to malaria therapy has been introduced which led to the discovery of noval metalcontaining aminoquinolines analogues viz. ferroquine (FQ or 1), Ruthenoquine (RQ or 2) and other related potent metal-analogues. It observed that some metal containing analogues (Fe-, Rh-, Ru-, Re-, Au-, Zn-, Cr-, Pd-, Sn-, Cd-, Ir-, Co-, Cu-, and Mn-aminoquines) were more potent; however, some were equally potent as Chloroquine (CQ) and 1. This is probably due to the intertion of metals in the CQ via various approaches, which might be a very attractive strategy to develop a SAR of novel metal containing antimalarials. Thus, this review aims to summarize the SAR of metal containing aminoquines towards the discovery of potent antimalarial hybrids to provide an insight for rational designs of more effective and less toxic metal containing amoniquines.

Using Sources In History Teaching

2021 ◽  
pp. 54-67
Author(s):  
Seema S.Ojha
Keyword(s):  
Deductive Reasoning ◽  
Primary Source ◽  
Primary Sources ◽  
Historical Knowledge ◽  
History Teaching ◽  
Secondary Sources ◽  
The Past ◽  
Teaching History ◽  
The World ◽  
Source Materials

History is constructed by people who study the past. It is created through working on both primary and secondary sources that historians use to learn about people, events, and everyday life in the past. Just like detectives, historians look at clues, sift through evidence, and make their own interpretations. Historical knowledge is, therefore, the outcome of a process of enquiry. During last century, the teaching of history has changed considerably. The use of sources, viz. textual, visual, and oral, in school classrooms in many parts of the world has already become an essential part of teaching history. However, in India, it is only a recent phenomenon. Introducing students to primary sources and making them a regular part of classroom lessons help students develop critical thinking and deductive reasoning skills. These will be useful throughout their lives. This paper highlights the benefits of using primary source materials in a history classroom and provides the teacher, with practical suggestions and examples of how to do this.

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