Synthesis, Molecular Docking and Anticancer Activity of Some 5‐Aryl‐5, 10‐dihydropyrido[2, 3‐d:6, 5‐d′]dipyrimidine‐2, 4, 6, 8‐tetraone Derivatives and Pyrido[2, 3‐d]pyrimidines. Issue 7 (17th February 2022)

• Record Type: Journal Article
• Authors: Farag, Basant; Agili, Fatimah; El‐Kalyoubi, Samar; Said, Said A.; Youssif, Shaker; Shehta, Wael
• Is Part Of: ChemistrySelect. Volume 7:Issue 7(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-17
• Subjects: 6-Aminouracil -- Anticancer activity -- pyridodipyrimidines -- pyridopyrimidines -- molecular modeling; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202103834
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A novel and efficient route towards the synthesis of pyrido[2, 3‐ d :6, 5‐ d′ ]dipyrimidines 4 a –g as unexpected products through the reaction of 6‐aminouracil (1 ) and arylidenemalononitrile or ethyl arylidenecyanoacetate in acetic acid were investigated. On the other hand, reaction of 6‐aminouracil and ethyl 4‐nitrobenzylidenecyanoacetate in ethanol in presence of piperidine (few drops) afforded pyrido[2, 3‐ d ]pyrimidine‐6‐carbonitrile 5 . In addition, pyrido[2, 3‐ d ]pyrimidines 6 a –g were obtained through the reaction of 5 with different aliphatic amines in ethanol in presence of triethylamine (few drops). All reactions proceeded in good to excellent yields and the resulting compounds were characterized by different spectroscopic techniques. The antiproliferative activity of these compounds was evaluated towards HEPG‐2, MCF‐7 and HCT‐116 cell lines. The compound 6 a displayed the highest activity against the tested cell lines, followed by compound 6 d, 6 g and 6 b, with strong affinity to bind with the active and allosteric sites of topoisomerase II, as authenticated from the molecular docking analyses. Abstract : In this article, we describe a novel and efficient route for the synthesis of pyridodipyrimidines 4 a –g. The synthesized compounds 4 a –g and pyridopyrimidines 6 a –g were evaluated as anti‐cancer agents in vitro in comparison to 5‐FU, MTX and DOX against HEPG‐2, MCF‐7 and HCT‐116 cell lines. The compound 6 a displayed the highest antiproliferative activity, followed by compound 6 d, 6 g and 6 b with strong affinity to bind with topoisomerase II active and allosteric sites, as revealed from the molecular docking analyses.