Pyrazolyl-Ureas as Interesting Scaffold in Medicinal Chemistry

The pyrazole nucleus has long been known as a privileged scaffold in the synthesis of biologically active compounds. Within the numerous pyrazole derivatives developed as potential drugs, this review is focused on molecules characterized by a urea function directly linked to the pyrazole nucleus in a different position. In the last 20 years, the interest of numerous researchers has been especially attracted by pyrazolyl-ureas showing a wide spectrum of biological activities, ranging from the antipathogenic activities (bacteria, plasmodium, toxoplasma, and others) to the anticarcinogenic activities. In particular, in the anticancer field, pyrazolyl-ureas have been shown to interact at the intracellular level on many pathways, in particular on different kinases such as Src, p38-MAPK, TrKa, and others. In addition, some of them evidenced an antiangiogenic potential that deserves to be explored. This review therefore summarizes all these biological data (from 2000 to date), including patented compounds.

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One-pot Synthesis of Pyrano[2,3-c]pyrazole Derivatives via Multicomponent Reactions (MCRs) and their Applications in Medicinal Chemistry

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x19666211220141622 ◽

2021 ◽

Vol 19 ◽

Author(s):

Swapan Kumar Biswas ◽

Debasis Das

Keyword(s):

Multicomponent Reactions ◽

Medicinal Chemistry ◽

Biological Activities ◽

Biologically Active ◽

Pyrazole Derivatives ◽

One Pot ◽

Discovery Research ◽

Drug Discovery Research ◽

Biological Interest ◽

Derivatives Of

Background: Many pyrano[2,3-c]pyrazole derivatives display diverse biological activities and some of them are known as anticancer, analgesic, anticonvulsant, antimicrobial, anti-inflammatory, and anti-malarial agents. In recent years, easy convergent, multicomponent reactions (MCRs) have been adopted to make highly functionalizedpyrano[2,3-c]pyrazole derivatives of biological interest. The synthesis of 1,4-dihydropyrano[2,3-c]pyrazole (1,4-DHPP, 2), 2,4-dihydropyrano[2,3-c]pyrazole (2,4-DHPP, 3), 4-hydroxypyrano[2,3-c]pyrazole (4-HPP, 4) derivatives, 1,4,4-substitied pyranopyrazole (SPP, 5) were reported via two-, three-, four- and five-component reactions (MCRs). Methods: This review article compiles the preparation of pyrano[2,3-c]pyrazole derivatives, and it highlights the applications of various pyrano[2,3-c]pyrazole derivatives in medicinal chemistry. Results: Varieties of pyrano[2,3-c]pyrazole derivatives were achieved via “One-pot” multicomponent reactions (MCRs). Different reaction conditions in the presence of a catalyst or without catalysts were adapted to prepare the pyrano[2,3-c]pyrazole derivatives. Conclusion: Biologically active pyrano[2,3-c]pyrazole derivatives were prepared and used in drug discovery research.

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Recent Advances on Quinazoline Derivatives: A Potential Bioactive Scaffold in Medicinal Chemistry

ChemEngineering ◽

10.3390/chemengineering5040073 ◽

2021 ◽

Vol 5 (4) ◽

pp. 73

Author(s):

Ram Karan ◽

Pooja Agarwal ◽

Mukty Sinha ◽

Neelima Mahato

Keyword(s):

Heterocyclic Compounds ◽

Medicinal Chemistry ◽

Biological Activities ◽

Therapeutic Agents ◽

Biologically Active Compounds ◽

Biologically Active ◽

Active Compounds ◽

Diverse Range ◽

Important Group ◽

Quinazoline Derivatives

This paper intended to explore and discover recent therapeutic agents in the area of medicinal chemistry for the treatment of various diseases. Heterocyclic compounds represent an important group of biologically active compounds. In the last few years, heterocyclic compounds having quinazoline moiety have drawn immense attention owing to their significant biological activities. A diverse range of molecules having quinazoline moiety are reported to show a broad range of medicinal activities like antifungal, antiviral, antidiabetic, anticancer, anti-inflammatory, antibacterial, antioxidant and other activities. This study accelerates the designing process to generate a greater number of biologically active candidates.

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Methyl linked pyrazoles: Synthetic and Medicinal Perspective

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210914124914 ◽

2021 ◽

Vol 21 ◽

Author(s):

Tulika Sharma ◽

Joginder Singh ◽

Bijender Singh ◽

Ramesh Kataria ◽

Vinod Kumar

Keyword(s):

Medicinal Chemistry ◽

Biological Activities ◽

Wide Spectrum ◽

Review Article ◽

Present Review ◽

Pyrazole Derivatives ◽

High Efficacy ◽

Depth Analysis ◽

Synthetic Approaches ◽

Substituted Pyrazoles

: Pyrazoles, an important and well known class of the azole family, have been found to show a large number of applications in various fields specially of medicinal chemistry. Among pyrazole derivatives, particularly, methyl substituted pyrazoles have been reported as the potent medicinal scaffolds that exhibit a wide spectrum of biological activities. The present review is an attempt to highlight the detailed synthetic approaches for methyl substituted pyrazoles along with in depth analysis of their respective medical significances till March2021. It is hoped that literature sum-up in the form of present review article would certainly be a great tool to assist the medicinal chemists for generating new leads possessing pyrazole nucleus with high efficacy and less microbial resistance.

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Arylpyrazoles: Heterocyclic Scaffold of Immense Therapeutic Application

Current Organic Chemistry ◽

10.2174/1570179417999200628035645 ◽

2020 ◽

Vol 24 (14) ◽

pp. 1555-1581

Author(s):

Garima Tripathi ◽

Anil Kumar Singh ◽

Abhijeet Kumar

Keyword(s):

Biological Activities ◽

Biologically Active ◽

Present Review ◽

Pyrazole Derivatives ◽

Therapeutic Application ◽

Diverse Range ◽

Major Class ◽

Anti Inflammatory

Among the major class of heterocycles, the N-heterocycles, such as pyrazoles, are scaffolds of vast medicinal values. Various drugs and other biologically active molecules are known to contain these N-heterocycles as core motifs. Specifically, arylpyrazoles have exhibited a diverse range of biological activities, including anti-inflammatory, anticancerous, antimicrobial and various others. For instance, arylpyrazoles are present as core moieties in various insecticides, fungicides and drugs such as Celebrex and Trocoxil. The present review will be highlighting the significant therapeutic importance of pyrazole derivatives developed in the last few years.

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Substituted Pyrazoles and Their Heteroannulated Analogs—Recent Syntheses and Biological Activities

Molecules ◽

10.3390/molecules26164995 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4995

Author(s):

Mohamed Ramadan ◽

Ashraf A. Aly ◽

Lamiaa E. Abd El-Haleem ◽

Mohammed B. Alshammari ◽

Stefan Bräse

Keyword(s):

Medicinal Chemistry ◽

Biological Activities ◽

Biologically Active ◽

Substituted Pyrazoles ◽

Privileged Scaffolds

Pyrazoles are considered privileged scaffolds in medicinal chemistry. Previous reviews have discussed the importance of pyrazoles and their biological activities; however, few have dealt with the chemistry and the biology of heteroannulated derivatives. Therefore, we focused our attention on recent topics, up until 2020, for the synthesis of pyrazoles, their heteroannulated derivatives, and their applications as biologically active moieties. Moreover, we focused on traditional procedures used in the synthesis of pyrazoles.

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Co-Microencapsulation of Anthocyanins from Black Currant Extract and Lactic Acid Bacteria in Biopolymeric Matrices

Molecules ◽

10.3390/molecules25071700 ◽

2020 ◽

Vol 25 (7) ◽

pp. 1700 ◽

Cited By ~ 2

Author(s):

Iuliana Maria Enache ◽

Aida Mihaela Vasile ◽

Elena Enachi ◽

Vasilica Barbu ◽

Nicoleta Stănciuc ◽

...

Keyword(s):

Lactic Acid ◽

Lactic Acid Bacteria ◽

Biological Activities ◽

Biologically Active Compounds ◽

Biologically Active ◽

Confocal Laser ◽

In Vitro Digestibility ◽

Black Currant ◽

Active Compounds ◽

Food Ingredients

Anthocyanins from black currant extract and lactic acid bacteria were co-microencapsulated using a gastro-intestinal-resistant biocomposite of whey protein isolate, inulin, and chitosan, with an encapsulation efficiency of 95.46% ± 1.30% and 87.38% ± 0.48%, respectively. The applied freeze-drying allowed a dark purple stable powder to be obtained, with a satisfactory content of phytochemicals and 11 log colony forming units (CFU)/g dry weight of powder (DW). Confocal laser microscopy displayed a complex system, with several large formations and smaller aggregates inside, consisting of biologically active compounds, lactic acid bacteria cells, and biopolymers. The powder showed good storage stability, with no significant changes in phytochemicals and viable cells over 3 months. An antioxidant activity of 63.64 ± 0.75 mMol Trolox/g DW and an inhibitory effect on α-amylase and α-glucosidase of 87.10% ± 2.08% and 36.96% ± 3.98%, respectively, highlighted the potential biological activities of the co-microencapsulated powder. Significantly, the in vitro digestibility profile showed remarkable protection in the gastric environment, with controlled release in the intestinal simulated environment. The powder was tested by addition into a complex food matrix (yogurt), and the results showed satisfactory stability of biologically active compounds when stored for 21 d at 4 °C. The obtained results confirm the important role of microencapsulation in ensuring a high degree of protection, thus allowing new approaches in developing food ingredients and nutraceuticals, with enhanced functionalities.

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THE RED BLOOD CELLS CATALASE ACTIVITY IS INFLUENCED BY TARAXACUM OFFICINALE

InterConf ◽

10.51582/interconf.21-22.05.2021.020 ◽

2021 ◽

pp. 167-177

Author(s):

Ala Fulga ◽

Valeriana Pantea ◽

Svetlana Protopop ◽

Olga Tagadiuc ◽

Mihail Todiras ◽

...

Keyword(s):

Antioxidant Activity ◽

Catalase Activity ◽

Biological Activities ◽

Wide Spectrum ◽

Sesquiterpene Lactones ◽

Natural Antioxidants ◽

Taraxacum Officinale ◽

Biologically Active ◽

Ability To Act ◽

Leaves And Roots

Natural antioxidants protect cells against oxidative stress, which is directly involved in ageing processes and in the pathogenesis of cardiovascular, neurodegenerative and neoplastic diseases. Taraxacum officinale (TO) due to its rich content of biologically active ingredients has been commonly used in traditional medicine. It contains a wide spectrum of compounds with antioxidant activity. The content depends of parts of this plant. The roots are rich in phenolic and terpene compounds, sesquiterpene lactones, fructosans and inulin, while leaves are rich in substances belonging to flavonoids, phenolic acids, coumarins and vitamins, especially vitamin A. The literature results prove that antioxidant activity of TO depends on several factors including the plant part, the solvent used, as well as the duration of extraction. The aim of this study was to evaluate and to compare the action of alcoholic extracts of roots and leaves of TO on RBC’s catalase activity. Material and methods. Raw Taraxacum officinale plant material consisted of dried leaves and roots were harvested from a natural site. The extracts for analysis were prepared using 20, 25, 40, 50 and 80% (v/v) ethanol mixtures used as solvents. The catalase activity was established by using RBC of healthy persons. Conclusions. Phytotherapeutic herbs and plants continue to play an important role in the discovery and development of drugs. Leaves and roots of dandelion represent a rich source of bioactive compounds for potential exploitation in nutraceuticals and pharmacological sectors. Taraxacum officinale has a high ability to act as an antioxidant. The highest influence on RBC’s catalase activity was reported in case of roots ethanolic extracts of 25%. These actions are realized due to multiple substances, whose content probably depends of ethanol’s concentration. Additional studies are needed to characterize biological activities of these extracts.

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Cryptic Host Defense Peptides: Multifaceted Activity and Prospects for Medicinal Chemistry

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200325112425 ◽

2020 ◽

Vol 20 (14) ◽

pp. 1274-1290

Author(s):

Bruna de Oliveira Costa ◽

Octávio Luiz Franco

Keyword(s):

Host Defense ◽

Medicinal Chemistry ◽

Biological Activities ◽

Proteolytic Processing ◽

Biologically Active ◽

Host Defense Peptides ◽

Clinical Phase ◽

Evolutionarily Conserved ◽

Defense Peptides ◽

Endogenous Precursor

Host defense peptides (HDPs) comprise a heterogeneous group of evolutionarily conserved and biologically active small molecules that are produced by different organisms. HDPs are widely researched because they often have multiple biological activities, for example antimicrobial, immunomodulatory and anticancer activity. In this context, in this review we focus on cryptic HDPs, molecules derived specifically from proteolytic processing of endogenous precursor proteins. Here, we explore the biological activity of such molecules and we further discuss the development of optimized sequences based on these natural cryptic HDPs. In addition, we present clinical-phase studies of cryptic HDPs (natural or optimized), and point out the possible applicability of these molecules in medicinal chemistry.

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Biological Significance of Imidazole-based Analogues in New Drug Development

Current Drug Discovery Technologies ◽

10.2174/1570163816666190320123340 ◽

2020 ◽

Vol 17 (5) ◽

pp. 574-584 ◽

Cited By ~ 1

Author(s):

Pratiksha N. Chopra ◽

Jagdish K. Sahu

Keyword(s):

Medicinal Chemistry ◽

Biological Activities ◽

Biological Significance ◽

Water Soluble ◽

Biologically Active ◽

Bioactive Molecules ◽

Ring Structures ◽

Antibacterial And Antifungal ◽

Therapeutic Compounds ◽

Synthetic Medicinal

In the field of heterocyclic medicinal chemistry, especially five-membered ring structures containing a nitrogen atom, imidazole core is an imperative aromatic heterocycle which is usually present in naturally occurring products and synthetic bioactive molecules. The occurrence of imidazole moiety in therapeutic compounds may be beneficial in terms of improving water-soluble properties due to its two nitrogen atoms which leads to the creation of hydrogen bonds. The imidazole nucleus has also been recognized as an important isostere of triazole, pyrazole, thiazole, tetrazole, oxazole, amide etc. for the purpose of designing and development of various biologically active molecules. Moreover, imidazole core as an attractive binding site could interact with diverse cations and anions as well as biomolecules through different reactions in the human biological system thus displaying extensive biological activities. This effort thoroughly provides a wide-ranging assessment in current drug discovery and developments of imidazolebased analogues in the entire series of synthetic medicinal chemistry as antibacterial and antifungal, anticancer, anti-tubercular, analgesic and anti-inflammatory, anti-neuropathic, antihypertensive, anti-allergic, anti-parasitic, antiviral, antidepressant, anti-obesity and so on, altogether with their prospective approaches in diagnostic and pathological field. It is expected that the present review will be supportive on behalf of new opinions in the search for rational strategies of more efficacious and less toxic medicinal agents and drugs containing imidazole core.

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Bioinformatics approach on bioisosterism softwares to be used in drug discovery and development

Current Bioinformatics ◽

10.2174/1574893616666210525150747 ◽

2021 ◽

Vol 16 ◽

Author(s):

Nelson José Freitas da Silveira ◽

Walter Filgueira de Azevedo Jr. ◽

Rita Cardoso Guedes ◽

Leandro Marcos Santos ◽

Rodolfo Cabral Marcelino ◽

...

Keyword(s):

Drug Discovery ◽

Mode Of Action ◽

Wide Spectrum ◽

Chemical Properties ◽

Biologically Active Compounds ◽

Biologically Active ◽

New Drugs ◽

Active Compounds ◽

Research Areas ◽

Reduced Toxicity

Background: In the rational drug development field, a bioisosterism is a tool that improves lead compounds performance, reffering to molecular fragment substitution that has similar physical-chemical properties. Thus, it is possible to modulate drug properties such as absorption, toxicity, and half-life increase. This modulation is of pivotal importance in the discovery, development, identification, and interpretation of the mode of action of biologically active compounds. Objective: Our purpose here is to review the development and application of bioisosterism in drug discovery. In this study history, applications, and use of bioisosteric molecules to create new drugs with high binding affinity in the protein-ligand complexes are described. Method: It is an approach for molecular modification of a prototype based on the replacement of molecular fragments with similar physicochemical properties, being related to the pharmacokinetic and pharmacodynamic phase, aiming at the optimization of the molecules. Results: Discovery, development, identification, and interpretation of the mode of action of biologically active compounds are the most important factors for drug design. The strategy adopted for the improvement of leading compounds is bioisosterism. Conclusion: Bioisosterism methodology is a great advance for obtaining new analogs to existing drugs, enabling the development of new drugs with reduced toxicity, in a comparative analysis with existing drugs. Bioisosterism has a wide spectrum to assist in several research areas.

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