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

Abstract

A novel and efficient route towards the synthesis of pyrido [2,3d: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 4nitrobenzylidenecyanoacetate 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.

Design, Synthesis, Docking, 2D‐QSAR Modelling, Anticancer and Antioxidant Evaluation of Some New Azo‐Compounds Derivatives and Investigation of Their Fluorescence Properties

“…The compounds were elucidated by using IR, 1 H-NMR, 13 C-NMR and mass spectra, in addition to revealing their actual influence on human cancer (HEPG-2) and (MCF-7), antioxidant, antimicrobial, and fluoresceine properties, but the main biological activity on this protocol was as anticancer on human cancer (HEPG-2) and (MCF-7) and supported by docking studies due to these cells are the most frequent tumors in Egypt and more authentic cells, available for the cytotoxicity of compounds. [21] Some synthetized compound in this work showed the potent activity against cancer cell lines MCF-7 and HEPG2 cell so we also screen their effecting on the normal cell. The experimental data were provided by computational studies (molecular docking and 2D-QSAR modeling) by using MOE (2015).…”

Developments of pyridodipyrimidine heterocycles and their biological activities

“…Unexpectedly, Farag et al [ 82 ] efficiently prepared pyridodipyrimidines 46a – g (Scheme 23 ) in a one-step synthesis. Therefore, the reactions of 6-amino-uracil with arylidene-malononitrile or ethyl arylidene-cyanoacetate gave the desired products in respectable to exceptional yields.…”

“…The compounds are more applicable to hinder the growth of HePG2 cells in most of the cases except in the case of compounds 46b (Ar = 4-NO 2 -C 6 H 4 ) (IC 50 = 68.59 ± 3.6 µM), 46e (Ar = 4-MeO-C 6 H 4 ) (IC 50 = 42.63 ± 2.8 µM), and 46f (IC 50 = 35.91 ± 2.5 µM), against HCT-116 cells, along with the potency of compound 46 g (Ar = 4-OH-C 6 H 4 ) (IC 50 = 49.87 ± 3.0 µM) against MCF-7 tumor cells. The comparison of the cytotoxic results against the investigated cell lines with the chemotherapeutic standards indicated that the compounds displayed moderate to weak cytotoxic activities based on the scale of comparison that referred to the moderate impacts in the range of IC 50 = 21 to 50 µM along with the weak cytotoxic influences for IC 50 values higher than 50 µM [ 82 ].

Fig.

…”

Uracil: A Pharmacophore with Diverse Biological Potential

“…Farag et al [39] synthesised novel pyrido ). The synthesised compounds were appraised for its antiproliferative activity towards human hepatocarcinoma (HEPG-2), human colon carcinoma (HCT-116) and human mammary carcinoma (MCF-7) cell lines [40] It was observed that Anti HCV Kayali et al [23] Sofosbuvir 2.…”