Editors Choice Article | Novel Pyrazolo[3,4-d]pyrimidines as Potential Cytotoxic Agents: Design, Synthesis, Molecular Docking and CDK2 Inhibition

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry – Anti-Cancer Agents)

Author(s): Mai Maher, Asmaa E. Kassab*, Ashraf F. Zaher, Zeinab Mahmoud

 

 

Graphical Abstract:

 

Abstract:

Background: Pyrazolo[3,4-d]pyrimidine scaffold was reported to possess potent cytotoxic and CDK2 inhibitory activity as analogue of roscovitine.

Objective: To design and synthesize novel 1-(4-flourophenyl)pyrazolo[3,4-d]pyrimidine derivatives as bioisosters of roscovitine with potential cytotoxic and CDK2 inhibitory activity.

Methods: A series of novel 1-(4-flourophenyl)pyrazolo[3,4-d]pyrimidines were designed and synthesized. Structural elucidation for all the newly synthesized compounds was achieved through performing MS, 1H NMR, 13C NMR and IR spectral techniques. Eight compounds were screened for their cytotoxic activity by National Cancer Institute (USA) against 60 different human cancer cell lines. Compounds 2a, 4, 6, 7b, 8a and 8b were further studied through the determination of their IC50 values against the most sensitive cell lines. The inhibitory activities of compounds 2a and 4 were evaluated against CDK2 enzyme.
Results: Compound 4 exhibited the most prominent broad-spectrum cytotoxic activity against 42 cell lines representing all human cancer types showing growth inhibition percentages from 53.19 to 99.39. Compound 2a showed promising selectivity against several cell lines. Moreover, all the test compounds exhibited potent cytotoxic activity in nanomolar to micromolar range with IC50 values ranging from 0.58 to 8.32μM. Compound 2a showed significant cytotoxic activity against CNS (SNB-75), lung (NCI-H460) and ovarian (OVCAR-4) cancer cell lines with IC50 values 0.64, 0.78 and 1.9μM, respectively. Compound 4 showed promising potency against leukemia (HL-60) and CNS (SNB-75) cell lines (IC50 = 0.58 and 0.94μM, sequentially). Moreover, the antiproliferative activities of compounds 2a and 4 appeared to correlate well with their ability to inhibit CDK2 at sub-micromolar level (IC50 = 0.69 and 0.67μM, respectively) that were comparable to roscovitine (IC50=0.44μM). The Molecular docking results revealed that compound 4 interacted with the same key amino acids as roscovitine in the active site of CDK2 enzyme with a marked docking score (-14.1031 kcal/mol).
Conclusion: 1-(4-Flourophenyl)pyrazolo[3,4-d]pyrimidine is a promising scaffold for the design and synthesis of potent cytotoxic leads.

To read out more, please visit: http://www.eurekaselect.com/171723/article

Become an Editorial Board Member (EBM) | Current Nutraceuticals

 

Current Nutraceuticals publishes original research articles, mini- and full-length reviews, feature articles, technical notes and thematic issues covering all aspects of nutraceuticals, from the isolation and comprehensive characterization of secondary metabolites and their synthesis to the biological activity of nutritional constituents and antioxidants, clinical, population, ethnological and agricultural studies. The journal also explicitly welcomes interdisciplinary contributions considering wider social, cultural, ethical and applied aspects of nutraceuticals and nutrition in modern society.

  • Isolation and comprehensive chemical and physical characterization of active ingredients
  • Secondary metabolites from plants and (micro-)organisms
  • Antioxidants
  • Chemoprevention
  • Biomarkers of nutrition and health
  • Chemistry of nutraceuticals, including synthesis
  • Nutrition and ageing
  • Nutrition and lifestyle
  • Nutraceuticals and drug development
  • Nutraceuticals in agriculture
  • Healthy diets
  • Nutraceuticals in Society: Wider cultural, social, ethical, ecological and economic implications

The Journal Current Nutraceuticals is interested in appointing active Editorial Board Member  on the Journal’s Board. If you are working in the related field as of the journal and are interested in becoming an Editorial Board Member, please send us your CV and a list of publications. If, however, the scope of the journal is not directly related to your field, you can recommend suitable colleagues for the same, and, if possible, send their CV along with their list of publications. Mention in the subject line, the field of interest and send your CV at: hermain@benthamscience.net and CC: faizan@benthamscience.net

 

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Aims & Scope | Letters in Organic Chemistry 

Letters in Organic Chemistry publishes original letters (short articles), research articles, full-length/mini-reviews and thematic issues based on mini-reviews and short articles, in all areas of organic chemistry including synthesis, bioorganic, medicinal, natural products, organometallic, supramolecular, molecular recognition and physical organic chemistry. The emphasis is to publish quality papers rapidly by taking full advantage of latest technology for both submission and review of the manuscripts.

The journal is an essential reading for all organic chemists belonging to both academia and industry. To learn more about the journal, please visit: https://benthamscience.com/journals/letters-in-organic-chemistry/

 

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Editor’s Choice Article | Synthesis, Molecular Modeling and Biological Evaluation of 5-arylidene- N,N-diethylthiobarbiturates as Potential α-glucosidase Inhibitors

 

Author(s): Momin Khan*, Sehrish Khan, Amir Ul Mulk, Anis Ur Rahman, Abdul Wadood, Sulaiman Shams, Muhammad Ashraf, Jameel Rahman, Iltaf Khan, Abdul Hameed, Zahid Hussain, Abbas Khan, Khair Zaman, Khalid M. Khan, Shahnaz Perveen.

Journal Name: Medicinal Chemistry

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Barbituric acid derivatives are a versatile group of compounds which are identified as potential pharmacophores for the treatment of anxiety, epilepsy and other psychiatric disorders. They are also used as anesthetics and have sound effects on the motor and sensory functions. Barbiturates are malonylurea derivatives with a variety of substituents at C-5 position showing resemblance with nitrogen and sulfur containing compounds like thiouracil which exhibited potent anticancer and antiviral activities. Recently, barbituric acid derivatives have also received great interest for applications in nanoscience. Read out full article here: http://www.eurekaselect.com/165349/article

Aims & Scope | Protein & Peptide Letters

Aims & Scope

 

Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations.

Protein & Peptide Letters focuses on:

  • Structure Studies
  • Advances in Recombinant Expression
  • Drug Design
  • Chemical Synthesis
  • Function
  • Pharmacology
  • Enzymology
  • Conformational Analysis
  • Immunology
  • Biotechnology
  • Protein Engineering
  • Protein Folding
  • Sequencing
  • Molecular Recognition
  • Purification and Analysis

 

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Read out more at:  https://benthamscience.com/journals/protein-and-peptide-letters/aims-scope/#top

OPEN ACCESS ARTICLE – The Role of Phosphorus Trichloride and Phosphorous Acid in the Formation of α-Hydroxymethylenebisphosphonic Acids from the Corresponding Carboxylic Acids – A Mechanistic Overview

Journal Name: Current Organic Chemistry

Author(s): Dávid Illés Nagy, Alajos Grün, István Greiner, Gyorgy Keglevich*.

 

 

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Abstract:

Background: Although the synthesis of α-hydroxymethylenebisphosphonic acids (dronic acids) and derivatives by reaction of the corresponding carboxylic acids (or its derivatives) with P-reagents, such as phosphorus trichloride, phosphorous acid and phosphoryl chloride formed the subject of many studies, in most cases, the selection of the P-reagents, their ratio, and the conditions (solvent and temperature) were not optimized.

Method: Selection of the appropriate P-reagents and their ratios, along with the conditions is possible, only if the reaction protocol (sequence of the steps) or the mechanism is known. For this purpose, the relevant information was extracted from the literature, critically discussed and the conclusions were drawn. Our own experiences are also summarized on the possible mechanisms, and on the related optimum set of the reaction parameters depending mainly on the nature of the solvent used.

Conclusion: This review gives a better understanding of the dronate chemistry, and promotes “greener” and more practical syntheses.

 

Read more here: http://www.eurekaselect.com/151654

Testimonial bY MD YOUSUF ANSARI!

 

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Contributed Article: “Synthesis, cytotoxic evaluation, and molecular docking studies of new oxadiazole analogues

OPEN ACCESS ARTICLE – The Role of Phosphorus Trichloride and Phosphorous Acid in the Formation of α-Hydroxymethylenebisphosphonic Acids from the Corresponding Carboxylic Acids – Current Organic Chemistry

Journal: Current Organic Chemistry

Author(s): Dávid Illés Nagy, Alajos Grün, István Greiner, Gyorgy Keglevich

Graphical Abstract:

 

Abstract:

Background: Although the synthesis of α-hydroxymethylenebisphosphonic acids (dronic acids) and derivatives by reaction of the corresponding carboxylic acids (or its derivatives) with P-reagents, such as phosphorus trichloride, phosphorous acid and phosphoryl chloride formed the subject of many studies, in most cases, the selection of the P-reagents, their ratio, and the conditions (solvent and temperature) were not optimized.

Method: Selection of the appropriate P-reagents and their ratios, along with the conditions is possible, only if the reaction protocol (sequence of the steps) or the mechanism is known. For this purpose, the relevant information was extracted from the literature, critically discussed and the conclusions were drawn. Our own experiences are also summarized on the possible mechanisms, and on the related optimum set of the reaction parameters depending mainly on the nature of the solvent used.

Conclusion: This review gives a better understanding of the dronate chemistry, and promotes “greener” and more practical syntheses.

 

EDITOR’S CHOICE – New Prolinamides with Isosteviol Skeleton as Efficient Organocatalysts for the Direct Asymmetric Aldol Reaction – Letters in Organic Chemistry

Journal: Letters in Organic Chemistry

Author(s): Yu-Xia Liu*, Zhi-Wei Ma, Yan-Xun Li, Jing-Chao Tao

Graphical Abstract:

 

Abstract:

In this work, two new prolinamides with isosteviol skeleton were synthesized and used as chiral catalysts for the asymmetric aldol reaction. Solvent effects, catalyst loading, substrate scope and the influence of water on the reaction were investigated. With only 5 mol % loading, the synthesized catalysts showed excellent activity (up to 98% yield) and good stereoselectivity (up to 87:13 dr, 90% ee) for the direct aldol reaction of cyclohexanone and substituted benzaldehydes at room temperature.

Read more here: http://www.eurekaselect.com/158630/article

 

 

EDITOR’S CHOICE – PHOTOCHEMICAL REACTIONS – CURRENT ORGANIC SYNTHESIS

Journal: Current Organic Synthesis

Author(s): Navjeet Kaur

Graphical Abstract:

 

Abstract:

Background: Chemists have been interested in light as an energy source to induce chemical reactions since the beginning of scientific chemistry. The organic photochemical reactions do not require toxic or polluting reagents so these reactions presented perspectives in the context of green chemistry and sustainable processes.

Objective: The largest classical divisions of organic chemistry are constituted by heterocycles. The role of heterocyclic compounds in a number of areas cannot be ignored. That’s why the chemists are continuously trying to design and synthesize heterocycles. This review summarizes the chemistry of photochemical reactions with emphasis on their synthetic applications. In this review, the most important photochemical transformations that have been employed in six-membered N-heterocycles synthesis are presented.

Conclusion: This review discussed the research activities in organic photochemistry that are applicable in organic synthesis. This review outlined the synthesis of heterocyclic compounds. Traditional approaches require highly specialized or expensive equipment, are highly inconvenient, or would be of limited use to the synthetic organic chemist. Therefore, these have been omitted by them. Photochemistry can be used to prepare a number of heterocycles selectively, efficiently and in high yield.

Read more here: http://www.eurekaselect.com/149678/article

 

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