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.

scholarly journals Palladium-Catalysed Synthesis and Transformation of Quinolones

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 228 ◽  
Author(s):  
Vera L. M. Silva ◽  
Artur M. S. Silva
Keyword(s):  
Multiple Bond ◽  
Single Step ◽  
Molecular Structures ◽  
Synthetic Methods ◽  
Complex Molecules ◽  
Bond Forming ◽  
Drug Candidates ◽  
Rapid Construction ◽  
Wide Range ◽  
Privileged Structures

Palladium-catalysed reactions have had a large impact on synthetic organic chemistry and have found many applications in target-oriented synthesis. Their widespread use in organic synthesis is due to the mild conditions associated with the reactions together with their tolerance of a wide range of functional groups. Moreover, these types of reactions allow the rapid construction of complex molecules through multiple bond-forming reactions in a single step, the so-called tandem processes. Pd-catalysed reactions have been applied to the synthesis of a large number of natural products and bioactive compounds, some of them of complex molecular structures. This review article aims to present an overview of the most important Pd-catalysed reactions employed in the synthesis and transformations of quinolin-2(1H)-ones and quinolin-4(1H)-ones. These compounds are widely recognized by their diverse bioactivity, being privileged structures in medicinal chemistry and useful structural moieties for the development of new drug candidates. Furthermore, they hold significant interest due to their host–guest chemistry; applications in chemical, biochemical and environmental analyses and use in the development of new synthetic methods. In some cases, the quinolone formation step cannot be ascribed to a claimed Pd-catalysed reaction but this reaction is crucial to get the appropriate substrate for cyclization into the quinolone. Herein we present and discuss different economical, efficient and selective synthetic strategies to access quinolone-type compounds.

3,4-Dihydroisocoumarins, Interesting Natural Products: Isolation, Organic Syntheses and Biological Activities

2019 ◽  
Vol 16 (1) ◽  
pp. 112-129 ◽  
Author(s):  
Aurelio Ortiz ◽  
Miriam Castro ◽  
Estibaliz Sansinenea
Keyword(s):  
Natural Products ◽  
Biological Activities ◽  
Natural Compounds ◽  
Biologically Active ◽  
Bacterial Strains ◽  
Drug Candidates ◽  
Heterocyclic Molecules ◽  
Naturally Occurring ◽  
Wide Range ◽  
Different Sources

Background:3,4-dihydroisocoumarins are an important small group belonging to the class of naturally occurring lactones isolated from different bacterial strains, molds, lichens, and plants. The structures of these natural compounds show various types of substitution in their basic skeleton and this variability influences deeply their biological activities. These lactones are structural subunits of several natural products and serve as useful intermediates in the synthesis of different heterocyclic molecules, which exhibit a wide range of biological activities, such as anti-inflammatory, antiplasmodial, antifungal, antimicrobial, antiangiogenic and antitumoral activities, among others. Their syntheses have attracted attention of many researchers reporting many synthetic strategies to achieve 3,4-dihydroisocoumarins and other related structures. </P><P> Objective: In this context, the isolation of these natural compounds from different sources, their syntheses and biological activities are reviewed, adding the most recent advances and related developments.Conclusion:This review aims to encourage further work on the isolation and synthesis of this class of natural products. It would be beneficial for synthetic as well as the medicinal chemists to design selective, optimized dihydroisocoumarin derivatives as potential drug candidates, since dihydroisocoumarin scaffolds have significant utility in the development of therapeutically relevant and biologically active compounds.

scholarly journals HYBRID MOLECULES BASED ON ALKALOIDS

2021 ◽  
Vol 3 ◽  
pp. 67-82
Author(s):  
O.A. Nurkenov ◽  
◽  
S.D. Fazylov ◽  
G.K. Mukusheva ◽  
Ye.V. Minayeva ◽  
...  
Keyword(s):  
Biologically Active ◽  
Plant Metabolites ◽  
New Methods ◽  
Hybrid Molecules ◽  
Wide Range ◽  
Methods Of Synthesis ◽  
Low Toxicity ◽  
Leading Compounds ◽  
Diverse Biological Activity

This review has been summarized the data on the synthesis of new hybrid derivatives based on alkaloid molecules. At the same time, there have been analyzed methods for obtaining hybrid structures containing fragments of natural compounds molecules in combination with other biologically active plant metabolites, as leading compounds for the development of new pharmacologically valuable agents, with the aim of creating new original drugs. The combination of pharmacophoric residues in one molecule, namely various aromatic and heterocyclic substituents in the nucleoside position of natural alkaloids, opens up new possibilities for both the subsequent chemical modification of the polyfunctional derivatives obtained and their new diverse biological activity. Effective methods of synthesis have been developed on the basis of directed transformations of these compounds (or their precursors). A wide range of pharmaco-logical properties of combined compounds of these series with a combination of low toxicity is promising. Considering that the preparation of combined derivatives based on alkaloid molecules has been insufficiently studied, the targeted synthesis of new com-pounds is of interest both in terms of new medicinespreparation and the development of new methods of organic synthesis, as well as the molecules stereochemistry determination of a new series of compounds.

scholarly journals The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 325 ◽  
Author(s):  
Floriana Cappiello ◽  
Maria Rosa Loffredo ◽  
Cristina Del Plato ◽  
Silvia Cammarone ◽  
Bruno Casciaro ◽  
...  
Keyword(s):  
Natural Products ◽  
Biologically Active ◽  
Antibiotic Resistant ◽  
Lead Compounds ◽  
Potential Development ◽  
Microbial Infections ◽  
New Antibiotics ◽  
Current Scenario ◽  
Resistant Strains ◽  
Unique Source

The discovery of antibiotics has revolutionized the medicine and treatment of microbial infections. However, the current scenario has highlighted the difficulties in marketing new antibiotics and an exponential increase in the appearance of resistant strains. On the other hand, research in the field of drug-discovery has revaluated the potential of natural products as a unique source for new biologically active molecules and scaffolds for the medicinal chemistry. In this review, we first contextualized the worldwide problem of antibiotic resistance and the importance that natural products of plant origin acquire as a source of new lead compounds. We then focused on terpenes and their potential development as antimicrobials, highlighting those studies that showed an activity against conventional antibiotic-resistant strains.

scholarly journals Spiro-Lactams as Novel Antimicrobial Agents

2020 ◽  
Vol 20 (2) ◽  
pp. 140-152 ◽  
Author(s):  
Américo J.S. Alves ◽  
Nuno G. Alves ◽  
Cátia C. Caratão ◽  
Margarida I.M. Esteves ◽  
Diana Fontinha ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Cycloaddition Reaction ◽  
Biologically Active ◽  
Biological Profile ◽  
Lead Compounds ◽  
Wide Range ◽  
Lactam Ring ◽  
Structural Modulation

Introduction: Structural modulation of previously identified lead spiro-β-lactams with antimicrobial activity was carried out. Objective: The main objective of this work was to synthesize and evaluate the biological activity of novel spiro-lactams based on previously identified lead compounds with antimicrobial activity. Methods: The target chiral spiro-γ-lactams were synthesized through 1,3-dipolar cycloaddition reaction of a diazo-γ-lactam with electron-deficient dipolarophiles. In vitro activity against HIV and Plasmodium of a wide range of spiro-β-lactams and spiro-γ-lactams was evaluated. Among these compounds, one derivative with good anti-HIV activity and two with promising antiplasmodial activity (IC50 < 3.5 µM) were identified. Results: A novel synthetic route to chiral spiro-γ-lactams has been established. The studied β- and γ- lactams were not cytotoxic, and three compounds with promising antimicrobial activity were identified, whose structural modulation may lead to new and more potent drugs. Conclusion: The designed structural modulation of biologically active spiro-β-lactams involved the replacement of the four-membered β-lactam ring by a five-membered γ-lactam ring. Although conformational and superimposition computational studies revealed no significant differences between β- and γ- lactam pharmacophoric features, the studied structural modulation did not lead to compounds with a similar biological profile. The observed results suggest that the β-lactamic core is a requirement for the activity against both HIV and Plasmodium.

Aspergillus sydowii Strain SCAU066 and Aspergillus versicolor Isolate BAB-6580: Potential Source of Xylanolytic, Cellulolytic and Amylolytic Enzymes

2020 ◽  
Vol 14 (2) ◽  
pp. 15
Author(s):  
Zaidah Zainal ariffin
Keyword(s):  
Extracellular Enzymes ◽  
Biologically Active ◽  
Aspergillus Versicolor ◽  
Aspergillus Sydowii ◽  
Aspergillus Tamarii ◽  
Alternative Source ◽  
Amylolytic Enzymes ◽  
Potato Dextrose Broth ◽  
Wide Range ◽  
Pharmaceutical Industries

Fungi is known to produce a wide range of biologically active metabolites and enzymes. Enzymes produced by fungi are utilized in food and pharmaceutical industries because of their rich enzymatic profile. Filamentous fungi are particularly interesting due to their high production of extracellular enzymes which has a large industrial potential. The aim of this study is to isolate potential soil fungi species that are able to produce functional enzymes for industries. Five Aspergillus species were successfully isolated from antibiotic overexposed soil (GPS coordinate of N3.093219 E101.40269) by standard microbiological method. The isolated fungi were identified via morphological observations and molecular tools; polymerase chain reactions, ITS 1 (5’- TCC GTA GGT GAA CCT GCG G3’) forward primer and ITS 4 (5’-TCC TCC GCT TAT TGA TAT GC-3’) reverse primer. The isolated fungi were identified as Aspergillus sydowii strain SCAU066, Aspergillus tamarii isolate TN-7, Aspergillus candidus strain KUFA 0062, Aspergillus versicolor isolate BAB-6580, and Aspergillus protuberus strain KAS 6024. Supernatant obtained via submerged fermentation of the isolated fungi in potato dextrose broth (PDB) and extracted via centrifugation was loaded onto specific media to screen for the production of xylanolytic, cellulolytic and amylolytic enzymes. The present findings indicate that Aspergillus sydowii strain SCAU066 and Aspergillus versicolor isolate BAB-6580 have great potential as an alternative source of xylanolytic, cellulolytic and amylolytic enzymes.

The content of decenoic acids in drone brood preparations and combined preparations based on it

Biomics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 389-393
Author(s):  
D.V. Mitrofanov ◽  
N.V. Budnikova
Keyword(s):  
Royal Jelly ◽  
Storage Conditions ◽  
Water Soluble ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Strict Adherence ◽  
Drone Brood ◽  
Wide Range ◽  
Active Substances ◽  
Melanin Complex

The drone brood contains a large number of substances with antioxidant activity. These substances require stabilization and strict adherence to storage conditions. Among these substances are unique decenoic acids, the content of which is an indicator of the quality of drone brood and products based on it. The ability of drone brood to reduce the manifestations of oxidative stress is shown. There are dietary supplements for food and drugs based on drone brood, which are used for a wide range of diseases. Together with drone brood, chitosan-containing products, propolis, royal jelly can be used. They enrich the composition with their own biologically active substances and affect the preservation of the biologically active substances of the drone brood. Promising are the products containing, in addition to the drone brood, a chitin-chitosan-melanin complex from bees, propolis, royal jelly. The chitin-chitosan-melanin complex in the amount of 5% in the composition of the adsorbent practically does not affect the preservation of decenic acids, while in the amount of 2% and 10% it somewhat worsens. The acid-soluble and water-soluble chitosan of marine crustaceans significantly worsens the preservation of decenoic acids in the product. Drone brood with royal jelly demonstrates a rather high content of decenoic acids. When propolis is introduced into the composition of the product, the content of decenoic acids increases according to the content of propolis.

ASSESSMENT OF TOXICITY OF GERMANIUM COORDINATION COMPOUNDS

2019 ◽  
pp. 16-21
Author(s):  
A. V. Kadomtsevа ◽  
I. V. Zhdanovich ◽  
M. S. Piskunovа ◽  
A. N. Lineva ◽  
A. N. Novikova ◽  
...  
Keyword(s):  
Coordination Compounds ◽  
Organometallic Compounds ◽  
Biologically Active ◽  
Pharmacological Properties ◽  
Toxicological Studies ◽  
Methods Of Synthesis ◽  
Promising Area

The synthesis of biologically active coordination compounds and the design on their basis of effective pharmacological preparations is currently the promising area. This paper presents the results of the toxicological studies on digermanium and its complex derivatives. It should be noted that the positive medical properties of organometallic compounds of germanium are confirmed by numerous studies, therefore, the development of the methods of synthesis, as well as investigations of physicochemical and pharmacological properties of these compounds are at the center of attention.

Potential Triazole-based Molecules for the Treatment of Neglected Diseases

2019 ◽  
Vol 26 (23) ◽  
pp. 4403-4434 ◽  
Author(s):  
Susimaire Pedersoli Mantoani ◽  
Peterson de Andrade ◽  
Talita Perez Cantuaria Chierrito ◽  
Andreza Silva Figueredo ◽  
Ivone Carvalho
Keyword(s):  
Effective Treatment ◽  
Chagas Disease ◽  
Medicinal Chemistry ◽  
Biological Activities ◽  
Neglected Diseases ◽  
Triazole Derivatives ◽  
Wide Range ◽  
The World ◽  
Great Relevance ◽  
The Moment

Neglected Diseases (NDs) affect million of people, especially the poorest population around the world. Several efforts to an effective treatment have proved insufficient at the moment. In this context, triazole derivatives have shown great relevance in medicinal chemistry due to a wide range of biological activities. This review aims to describe some of the most relevant and recent research focused on 1,2,3- and 1,2,4-triazolebased molecules targeting four expressive NDs: Chagas disease, Malaria, Tuberculosis and Leishmaniasis.

Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier

2020 ◽  
Vol 26 (27) ◽  
pp. 3234-3250
Author(s):  
Sushil K. Kashaw ◽  
Prashant Sahu ◽  
Vaibhav Rajoriya ◽  
Pradeep Jana ◽  
Varsha Kashaw ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Biomedical Engineering ◽  
Viral Infections ◽  
Slow Release ◽  
Molecular Level ◽  
Release Kinetics ◽  
Biologically Active ◽  
Release Process ◽  
Rapid Release ◽  
Wide Range

Potential short interfering RNAs (siRNA) modulating gene expression have emerged as a novel therapeutic arsenal against a wide range of maladies and disorders containing cancer, viral infections, bacterial ailments and metabolic snags at the molecular level. Nanogel, in the current medicinal era, displayed a comprehensive range of significant drug delivery prospects. Biodegradation, swelling and de-swelling tendency, pHsensitive drug release and thermo-sensitivity are some of the renowned associated benefits of nanogel drug delivery system. Global researches have also showed that nanogel system significantly targets and delivers the biomolecules including DNAs, siRNA, protein, peptides and other biologically active molecules. Biomolecules delivery via nanogel system explored a wide range of pharmaceutical, biomedical engineering and agro-medicinal application. The siRNAs and DNAs delivery plays a vivacious role by addressing the hitches allied with chronic and contemporary therapeutic like generic possession and low constancy. They also incite release kinetics approach from slow-release while mingling to rapid release at the targets will be beneficial as interference RNAs delivery carriers. Therefore, in this research, we focused on the latest improvements in the delivery of siRNA loaded nanogels by enhancing the absorption, stability, sensitivity and combating the hindrances in cellular trafficking and release process.

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