ABSTRACT
A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines 3i and 3l, show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site.
Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Inflammation Mediators/antagonists & inhibitors , Pyrroles/chemistry , Pyrroles/pharmacology , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cytokines/antagonists & inhibitors , Cytokines/chemistry , Inflammation Mediators/chemistry , Male , Molecular Conformation , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Structure , Pyrimidines , Pyrroles/chemical synthesis , Rats , Structure-Activity RelationshipABSTRACT
OBJECTIVE: To investigate the antioxidant and anticancer activities of aqueous extracts of nine microalgal species. METHODS: Variable percentages of major secondary metabolites (total phenolic content, terpenoids and alkaloids) as well as phycobiliprotein pigments (phycocyanin, allophycocyanin and phycoerythrin) in the aqueous algal extracts were recorded. Antioxidant activity of the algal extracts was performed using 2, 2 diphenyl-1-picrylhydrazyl (DPPH) test and 2,2'- azino-bis (ethylbenzthiazoline-6-sulfonic acid (ABTS.(+)) radical cation assay. Anticancer efficiency of the algal water extracts was investigated against Ehrlich Ascites Carcinoma cell (EACC) and Human hepatocellular cancer cell line (HepG2). RESULTS: Antioxidant activity of the algal extracts was performed using DPPH test and ABTS.(+) radical cation assays which revealed 30.1-72.4% and 32.0-75.9% respectively. Anticancer efficiency of the algal water extracts was investigated against Ehrlich Ascites Carcinoma Cell (EACC) and Human Hepatocellular cancer cell line (HepG2) with an activity ranged 87.25% and 89.4% respectively. Culturing the promising cyanobacteria species; Nostoc muscorum and Oscillatoria sp. under nitrogen stress conditions (increasing and decreasing nitrate content of the normal BG11 medium, 1.5 g/L), increased nitrate concentration (3, 6 and 9 g/L) led to a remarkable increase in phycobilin pigments followed by an increase in both antioxidant and anticancer activities in both cyanobacterial species. While the decreased nitrate concentration (0.75, 0.37 and 0.0 g/L) induced an obvious decrease in phycobilin pigments with complete absence of allophycocyanin in case of Oscillatoria sp. CONCLUSIONS: Nitrogen starvation (0.00 g/L nitrate) induced an increase and comparable antioxidant and anticancer activities to those cultured in the highest nitrate content.
