Synthesis and Evaluation of Acetylcholinesterase Inhibitory and Cytotoxic Activities of Pyrano[2,3-d]pyrimidines

Abstract

Objective: The study was conducted to evaluate the in vitro acetylcholinesterase (AchE) inhibition activity of novel pyrano[2,3- d]pyrimidine derivatives. Methods: A series of new pyrano[2,3- d]pyrimidine derivatives were synthesized in moderate to good yields (63%-81%) by using microwave-prompted “one-pot” two-step multicomponent reactions of cyclohexane-1,3-dione, malononitrile, aldehydes, and acetic anhydride. Noticeably, Diazabicyclo[2.2.2]octane was successfully employed as a basic catalyst for the formation of 2-amino-4H-pyran-3-carbonitrile intermediates. These products were identified using spectral data, and assessed in terms of their AChE inhibition activity and cytotoxicity against three types of human cancer cell lines including epidermoid carcinoma (KB), hepatoma carcinoma (HepG2), and non-small lung cancer (A549) cell lines. Results: Most of the products depicted moderate to good AChE inhibitory activity, among them, one product with methoxy moiety at meta-position on phenyl group showed the best AchE inhibition activity with IC50 values of 2.20 ± 0.17 µg/mL. Moreover, products exhibited no cytotoxicity against cancer cell lines. Conclusion: This study highlighted that pyrano[2,3- d]pyrimidine derivatives as promising candidates for further investigations directed to the discovery of new AChE inhibitors which could be used in Alzheimer's disease therapy.

Synthesis, molecular docking analysis and in vitro evaluation of new heterocyclic hybrids of 4-aza-podophyllotoxin as potent cytotoxic agents

“…20 Owing to the signicant role of heterocyclic ring systems in drug discovery and development, many studies have been undertaken to develop biologically active heterocyclic compounds. [21][22][23][24][25][26][27][28][29] Podophyllotoxin, an important plant-derived natural product, has several semisynthetic derivatives such as etoposide, teniposide and etophos, which have been employed in chemotherapy for various cancer types. 30 Although podophyllotoxin and its derivatives have been known as tubulin polymerization or DNA topoisomerase II inhibitors, they are too toxic for therapeutic use and causes some side effects.…”