Current medical approaches to control the Covid-19 pandemic are either to directly target the SARS-CoV-2
via
innovate a defined drug and a safe vaccine or indirectly target the medical complications of the virus. One of the indirect strategies for fighting this virus has been mainly dependent on using anti‐inflammatory drugs to control cytokines storm responsible for severe health complications. We revealed the discovery of novel fused pyrrolopyrimidine derivatives as promising antioxidant and anti-inflammatory agents. The newly synthesised compounds were evaluated for their in vitro anti-inflammatory activity using RAW264.7 cells after stimulation with lipopolysaccharides (LPS). The results revealed that
3a, 4b,
and
8e
were the most potent analogues. Molecular docking and simulations of these compounds against COX-2, TLR-2 and TLR-4 respectively was performed. The former results were in line with the biological data and proved that
3a, 4b
and
8e
have potential antioxidant and anti-inflammatory effects.
A series of benzo[
h
]chromenes, benzo[
f
]chromenes, and benzo[
h
]chromeno[2,3-
d
]pyrimidines were prepared. All the newly synthesised compounds were selected by National Cancer Institute for single-dose testing against 60 cell lines. Benzo[
h
]chromenes
5a
and
6a
showed promising anti-cancer activity and selected for the five-dose testing. Compounds
5a
and
6a
suppressed cell growth in HL-60 by the induction of cell cycle arrest, which was confirmed using flow cytometry and Annexin V-FITC/PI assays showed at the G1/S phase by regulating the expression of CDK-2/CyclinD1, triggering cell apoptosis by activating both the extrinsic (Fas/Caspase 8) and intrinsic (Bcl-2/Caspase 3) apoptosis pathways, which were determined by the western blot. Benzo[
h
]chromenes
5a
and
6a
decreased the protein expression levels of Bcl-2, CDK-2, and CyclinD1 and increased the expression of caspase 3, caspase 8, and Fas.
In silico
molecular analysis of compounds
5a
and
6a
in CDK-2 and Bcl-2 was performed.
For several decades, interest in pyrrole and pyrrolopyrimidine derivatives increases owing to their biological importance, such as anti-tumor, anti-microbial, anti-inflammatory, anti-diabetic, anti-histaminic, anti-malarial, anti-Parkinson, antioxidant and anti-viral, specially recently against COVID-19. These tremendous biological features motivated scientists to discover more pyrrole and fused pyrrole derivatives, owing to the great importance of the pyrrole nucleus as a pharmacophore in many drugs, and motivated us to present this article, highlighting on the different synthetic pathways of pyrrole and its fused compounds specially pyrrolopyrimidine, as well as their medicinal value from 2017 till 2021.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.