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.

Editor's Note

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Emily Kaliel
Keyword(s):  
Civil War ◽  
Public Memory ◽  
Historical Memory ◽  
Historical Analysis ◽  
Red River ◽  
Cultural Institutions ◽  
Economic Rights ◽  
The Past ◽  
Relationship Of

The articles published in our Fall 2016 edition are connected loosely under the themes of public memory and the uses of identity in the past. We are thrilled to present to you three excellent articles in our Fall 2016 edition: The article "Dentro de la Revolución: Mobilizing the Artist in Alfredo Sosa Bravo's Libertad, Cultura, Igualdad (1961)" analyzes Cuban artwork as multi-layered work of propaganda whose conditions of creation, content, and exhibition reinforce a relationship of collaboration between artists and the state-run cultural institutions of post-revolutionary Cuba; moving through fifty years of history “’I Shall Never Forget’: The Civil War in American Historical Memory, 1863-1915" provides a captivating look at the role of reconciliationist and emancipationist intellectuals, politicians, and organizations as they contested and shaped the enduring memory of the Civil War; and finally, the article “Politics as Metis Ethnogenesis in Red River: Instrumental Ethnogenesis in the 1830s and 1840s in Red River” takes the reader through a historical analysis of the development of the Metis identity as a means to further their economic rights. We wholly hope you enjoy our Fall 2016 edition as much as our staff has enjoyed curating it. Editors  Jean Middleton and Emily Kaliel Assistant Editors Magie Aiken and Hannah Rudderham Senior Reviewers Emily Tran Connor Thompson Callum McDonald James Matiko Bronte Wells

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.

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.

IV.—The Geological Development, Descent and Distribution of the Mammalia

1893 ◽  
Vol 10 (9) ◽  
pp. 401-412 ◽  
Author(s):  
Karl A. von Zittel
Keyword(s):  
South America ◽  
The Past ◽  
Limited Experience ◽  
The World ◽  
Relationship Of ◽  
North And South America ◽  
The Relationship ◽  
North And South ◽  
Animal World

In a spirited treatise on the ‘Origin of our Animal World’ Prof. L. Rütimeyer, in the year 1867, described the geological development and distribution of the mammalia, and the relationship of the different faunas of the past with each other and with that now existing. Although, since the appearance of that masterly sketch the palæontological material has been, at least, doubled through new discoveries in Europe and more especially in North and South America, this unexpected increase has in most instances only served as a confirmation of the views which Rutimeyer advanced on more limited experience. At present, Africa forms the only great gap in our knowledge of the fossil mammalia; all the remaining parts of the world can show materials more or less abundantly, from which the course followed by the mammalia in their geological development can be traced with approximate certainty.

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 A review on the production, structure, bioactivities and applications of Tremella polysaccharides

2021 ◽  
Vol 35 ◽  
pp. 205873842110005
Author(s):  
Xia Ma ◽  
Meng Yang ◽  
Yan He ◽  
Chuntao Zhai ◽  
Chengliang Li
Keyword(s):  
Biologically Active ◽  
Research Progress ◽  
Research Trend ◽  
Production Structure ◽  
Health States ◽  
Preparation Methods ◽  
The Past ◽  
Structure Activity ◽  
Relationship Of ◽  
Active Natural

Tremella polysaccharide is known to be structurally unique and biologically active natural products, abundant and versatile in activities and applications in food industry, daily chemical industry and medicine industry. In order to improve the industrialisation of Tremella polysaccharide, the limitations of preparation and structure-activity relationship of Tremella polysaccharide were reviewed in this paper. The research progress of Tremella polysaccharide in the past 20 years was summarized from the sources, preparation methods, molecular structure, activity and application, and the research trend in the future was also prospected. The application prospect of Tremella polysaccharide in against multiple sub-health states was worth expecting.

scholarly journals Cardiorespiratory Functioning in Youth with Persistent Post-Concussion Symptoms: A Pilot Study

2021 ◽  
Vol 10 (4) ◽  
pp. 561
Author(s):  
Aliyah Snyder ◽  
Christopher Sheridan ◽  
Alexandra Tanner ◽  
Kevin Bickart ◽  
Molly Sullan ◽  
...  
Keyword(s):  
Processing Speed ◽  
Mean Value ◽  
Exhaled Breath ◽  
Post Injury ◽  
The Past ◽  
Neurobehavioral Outcomes ◽  
End Tidal ◽  
Relationship Of ◽  
The Relationship ◽  
End Tidal Co2

Dysregulation of the autonomic nervous system (ANS) may play an important role in the development and maintenance of persistent post-concussive symptoms (PPCS). Post-injury breathing dysfunction, which is influenced by the ANS, has not been well-studied in youth. This study evaluated cardiorespiratory functioning at baseline in youth patients with PPCS and examined the relationship of cardiorespiratory variables with neurobehavioral outcomes. Participants were between the ages of 13–25 in two groups: (1) Patients with PPCS (concussion within the past 2–16 months; n = 13) and (2) non-injured controls (n = 12). Capnometry was used to obtain end-tidal CO2 (EtCO2), oxygen saturation (SaO2), respiration rate (RR), and pulse rate (PR) at seated rest. PPCS participants exhibited a reduced mean value of EtCO2 in exhaled breath (M = 36.3 mmHg, SD = 2.86 mmHg) and an altered inter-correlation between EtCO2 and RR compared to controls. Neurobehavioral outcomes including depression, severity of self-reported concussion symptoms, cognitive catastrophizing, and psychomotor processing speed were correlated with cardiorespiratory variables when the groups were combined. Overall, results from this study suggest that breathing dynamics may be altered in youth with PPCS and that cardiorespiratory outcomes could be related to a dimension of neurobehavioral outcomes associated with poorer recovery from concussion.

RELATIONSHIP OF TAXA IN GENUS MEDICAGO AS REVEALED BY HYBRIDIZATION.: II. M. PIRONAE × M. DAGHESTANICA WITH REFERENCE TO M. SATIVA

1968 ◽  
Vol 10 (2) ◽  
pp. 454-459 ◽  
Author(s):  
K. Lesins ◽  
C. B. Gillies
Keyword(s):  
The Past ◽  
Relationship Of ◽  
Chromatin Bridges ◽  
Metaphase I

Medicago pironae Vis. and M. daghestanica Rupr. are related to the extent that viable F1 hybrids can be easily obtained. These species should, therefore, be grouped taxonomically closer than has been done in the past. Their relationship to M. sativa L. is more remote, as judged by failure in hybridization. The M. pironae × M. daghestanica F1 hybrids were completely self-sterile and sterile on backcrossing to both parents. Pollen of the hybrids was close to 100% protoplasm-empty. Meiosis proceeded irregularly in 55% of metaphase I and diakinesis cells. At AI and All chromatin bridges were observed in 65% and 90% of cells, respectively. At pachytene, strands of unequal lengths and different chromomere patterns indicated cryptic chromosomal or genie dissimilarities.

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.

Varicella and Cortisone

PEDIATRICS ◽  
1956 ◽  
Vol 18 (1) ◽  
pp. 160-162 ◽  
Author(s):  
ROBERT J. HAGGERTY ◽  
R. CANNON ELEY
Keyword(s):  
Infectious Diseases ◽  
Clinical Course ◽  
Medical Center ◽  
Post Mortem ◽  
The Past ◽  
Vesicle Fluid ◽  
Heart Blood ◽  
Cortisone Therapy ◽  
Relationship Of

In the past 2 years we have seen 2 patients at the Children's Medical Center, who, while receiving cortisone therapy, developed varicella and died following a state of shock within a few days after the appearance of the vesicles. Post-mortem examinations of these patients revealed hemorrhagic vesicles throughout all viscera. In 1 case the virus of varicella was grown from vesicle fluid, heart blood, and lung. Since fatalities from varicella in childhood are so rarely encountered, even by physicians with vast experience in the field of infectious diseases, and since the clinical course of the infection in these two patients was so fulminating, the possible relationship of cortisone administration was raised.

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