New Pyrimidines and Triazolopyrimidines as Antiproliferative and Antioxidants with Cyclooxygenase-1/2 Inhibitory Potential

Abstract

Aim: Cyclooxygenase-2 (COX-2) inhibition and scavenging-free radicals are important targets in cancer treatment. Materials & methods: Sulfanylpyrimidines and triazolopyrimidines were synthesized and evaluated as anticancer and antioxidant COX-1/2 inhibitors. Results: Compound 7 showed the same growth inhibitory activity as 5-fluorouracil against MCF-7. Compound 6f displayed broad-spectrum anticancer activity against the four tested cancer cell lines. Compounds 5b, 6a, 6c, 6d and 8 were found to be more active antioxidants than trolox. Compounds 6a, 6c, 6f and 8 revealed high COX-2 inhibitory activity and selectivity, which was confirmed by docking studies. Conclusion: Compound 6f could be considered as promising anticancer and antioxidant structural lead with COX-2 inhibition that deserve further derivatization and investigation.

Pyrimidine: a review on anticancer activity with key emphasis on SAR

“…Pyrimidines and triazolopyrimidines as antiproliferative agents exhibited COX-1/2 inhibitory potential. Compound 12 (IC 50 range = 8.68 ± 0.2 to 36.56 ± 0.9 μg/ml) displayed in vitro activity against cancer cell lines HepG-2, MCF-7, CaCo-2, and A549 alongside COX-2 inhibition using 5-FU as the reference drug [15]. Previously in a study, combretastatin bridged pyrimidine derivatives were tested for antitumor activity against the MCF-7 and A549 using MTT assay.…”

Research developments in the syntheses, anti-inflammatory activities and structure–activity relationships of pyrimidines

“…Generally, the mechanism of action of pyrimidine-based anti-inflammatory agents is associated with the inhibition of PGE 2 generated by COX enzymes. 71,72 Like other NSAIDs, pyrimidine-based anti-inflammatory agents function by suppressing the activity of COX-1 and COX-2 enzymes and thus reduce the generation of PGE 2 . 73,74 Sufficient investigations have been performed to discover new and more efficient pyrimidine-based anti-inflammatory agents that can inhibit the activity of COX enzymes.…”

Synthesis and Antioxidant Activities of Novel Pyrimidine Acrylamides as Inhibitors of Lipoxygenase: Molecular Modeling and In Silico Physicochemical Studies

“…A considerable number of clinically used drugs such as minoxidil, phenobarbital, primidone, zidovudine, stavudine, 5-flurouracil, methotrexate, imatinib, dasatinib, pazopanib, nilotinib, cytarabine, uramustine, tegafur, risperidone, sulfamethazine and trimethoprim contain the pyrimidine heterocyclic scaffold [ 14 , 15 ]. In recent years, diverse biological activities of pyrimidine derivatives, including anticancer [ 16 , 17 ], antibacterial [ 18 , 19 , 20 ], antifungal [ 21 ], antitubercular [ 21 , 22 ], antimalarial [ 23 ], antiviral [ 24 , 25 , 26 ], analgesic [ 27 ], antioxidant [ 28 , 29 ], anti-lipoxygenase [ 30 , 31 ] and anti-inflammatory activities have been reported [ 32 , 33 ]. Thus, the pyrimidine ring can be considered as a promising pharmacophoric scaffold for the synthesis of novel bioactive molecules for the treatment of various diseases.…”