AI Article Synopsis
Article Abstract
Background: Medicinal chemistry of pyrazolopyrimidine scaffolds substituted with different heterocyclic nuclei has attracted great attention due to their wide range of biological activities that have been reported. Pyrazolopyrimidine scaffold is an important privileged heterocycle nucleus in drug discovery.
Methods: All pharmacological activities of pyrazolopyrimidine scaffold have been mentioned, such as anticancer, anti-inflammatory, antihypertensive, antitubercular, antiviral, antibacterial, antifungal, antidiabetic, and anti-obesity agents. In addition, it was used in both osteoporosis and neurological disorders. The difference in potency and bioavailability of pyrazolopyrimidine derivatives refers to the substituent groups that can increase the activity against specific targets and enhance their selectivity.
Results: This review provides an overview of different synthetic pathways, structure activity relationships, and preclinical studies of pyrazolopyrimidine scaffolds substituted with a variety of heterocyclic nuclei, as well as it provides a discussion on the significant biological findings of these important scaffolds. In addition, it provides some insights on the different macromolecular targets that pyrazolopyrimidine scaffold can effectively work on, such as; cyclin dependent kinases; CDK2, CDK7, and CDK9, checkpoint kinases; CHK1 and CHK2 and their correlation with the anticancer activity, PI3Kα, transient receptor potential canonical 6, B-Raf kinase, Interleukin- 1 receptor-associated kinase 4, B-cell lymphoma 6, TRKA-C kinase, potent kDa ribosomal protein S6 kinase, colon cancer cell line (CaCo-2), domain receptor kinase (KDR), HepG-2 carcinoma cell, FLT3. The antibacterial activity against B. subtilis and E. coli and antifungal activity against C. albicans, C. tropicalis, A. niger, and A. clavatus are discussed.
Conclusion: This review provides an overview of the different pharmacological activities of the pyrazolopyrimidine scaffold and its correlation with chemical structure. Some exciting new developments in pyrazolopyrimidine scaffolds are also presented in this review.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1381612829666221102162000 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PROTAC-attractive site as a new target for suppressing P-glycoprotein activity.
Arch Biochem Biophys
December 2024
Laboratory of Molecular Pharmacology, St. Petersburg State Institute of Technology (Technical University), St. Petersburg, 190013, Russia.
P-glycoprotein (P-gp) plays an important role in the rapid release of various small molecule substances from the cell. In turn, inhibition of this efflux transporter is an attractive strategy for both overcoming chemoresistance and facilitating oral absorption of drugs or CNS drug delivery. In this work, we adopt an approach typical for PROteolysis Targeting Chimera (PROTAC), which is based on the artificial drawing together of the target protein to E3 ubiquitin ligase, to P-gp.
View Article and Find Full Text PDFE-pharmacophore and deep learning based high throughput virtual screening for identification of CDPK1 inhibitors of Cryptosporidium parvum.
Comput Biol Chem
October 2024
Department of Agricultural Convergence Technology, College of Agriculture and Life Science, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Republic of Korea; Department of Food Science and Technology, College of Agriculture and Life Sciences, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Republic of Korea. Electronic address:
Cryptosporidiosis, a prevalent gastrointestinal illness worldwide, is caused by the protozoan parasite Cryptosporidium parvum. Calcium-dependent protein kinase 1 (CpCDPK1), crucial for the parasite's life cycle, serves as a promising drug target due to its role in regulating invasion and egress from host cells. While potent Pyrazolopyrimidine analogs have been identified as candidate hit molecules, they exhibit limitations in inhibiting Cryptosporidium growth in cell culture, prompting exploration of alternative scaffolds.
View Article and Find Full Text PDFOptimization of pyrazolopyridine 4-carboxamides with potent antimalarial activity for which resistance is associated with the P. falciparum transporter ABCI3.
Eur J Med Chem
October 2024
The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia. Electronic address:
Emerging resistance to current antimalarials is reducing their effectiveness and therefore there is a need to develop new antimalarial therapies. Toward this goal, high throughput screens against the P. falciparum asexual parasite identified the pyrazolopyridine 4-carboxamide scaffold.
View Article and Find Full Text PDFMolecular docking approach for the design and synthesis of new pyrazolopyrimidine analogs of roscovitine as potential CDK2 inhibitors endowed with pronounced anticancer activity.
Bioorg Chem
June 2024
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562, Cairo, Egypt. Electronic address:
Cyclin-dependent kinase 2 (CDK2) is a vital protein for controlling cell cycle progression that is critically associated with various malignancies and its inhibition could offer a convenient therapeutic approach in designing anticancer remedies. Consequently, this study aimed to design and synthesize new CDK2 inhibitors featuring roscovitine as a template model. The purine ring of roscovitine was bioisosterically replaced with the pyrazolo[3,4-d]pyrimidine scaffold, in addition to some modifications in the side chains.
View Article and Find Full Text PDFN- and s-substituted Pyrazolopyrimidines: A promising new class of potent c-Src kinase inhibitors with prominent antitumor activity.
Bioorg Chem
April 2024
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC 1.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!