Synthesis, characterization and molecular docking studies of thiouracil derivatives as potent thymidylate synthase inhibitors and potential anticancer agents

El‐Naggar, Abeer M.; Abou‐El‐Regal, M. M.; El‐Metwally, Souad A.; Sherbiny, Farag F.; Eissa, Ibrahim H.

doi:10.1007/s11030-017-9776-1

Cited by 57 publications

(22 citation statements)

References 37 publications

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“…In continuation of our previous efforts of design and synthesis of new anticancer agents, [ 41–48 ] especially DNA intercalators and Topo II inhibitors, [ 14,49–51 ] ligand‐based drug design approach was considered. Accordingly, molecular hybridization of quinazoline and other effective antitumor moieties was performed to obtain more promising anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

Design and discovery of new 1,2,4‐triazolo[4,3‐c]quinazolines as potential DNA intercalators and topoisomerase II inhibitors

Alesawy

Al‐Karmalawy

Elkaeed

et al. 2020

Archiv der Pharmazie

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A new series of 1,2,4‐triazolo[4,3‐c]quinazoline derivatives was designed and synthesized as Topo II inhibitors and DNA intercalators. The cytotoxic effect of the new members was evaluated in vitro against a group of cancer cell lines including HCT‐116, HepG‐2, and MCF‐7. Compounds 14c, 14d, 14e, 14e, 15b, 18b, 18c, and 19b exhibited the highest activities with IC50 values ranging from 5.22 to 24.24 µM. Furthermore, Topo II inhibitory activities and DNA intercalating affinities of the most promising candidates were evaluated as a possible mechanism for the antiproliferative effect. The results of the Topo II inhibition and DNA binding tests were coherent with that of in vitro cytotoxicity. Additionally, the most promising compound 18c was analyzed in HepG‐2 cells for its apoptotic effect and cell cycle arrest. It was found that 18c can induce apoptosis and arrest the cell cycle at the G2–M phase. Finally, molecular docking studies were carried out for the designed compounds against the crystal structure of the DNA−Topo II complex as a potential target to explore their binding modes. On the basis of these studies, it was hypothesized that the DNA binding and/or Topo II inhibition would participate in the noted cytotoxicity of the synthesized compounds.

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Section: Introductionmentioning

confidence: 99%

Design and discovery of new 1,2,4‐triazolo[4,3‐c]quinazolines as potential DNA intercalators and topoisomerase II inhibitors

Alesawy

Al‐Karmalawy

Elkaeed

et al. 2020

Archiv der Pharmazie

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“…In continuation of our research efforts toward the development of green synthetic methodologies for synthesis of new heterocyclic compounds with anticipated biological activities [] particularly which contain pyrimidine moiety [], herein, it is reported a highly efficient method for the synthesis of a novel series of biologically active pyrimidine derivatives which have been evaluated for their performed anticancer activities.…”

Section: Discussionmentioning

confidence: 99%

Eco‐friendly synthesis of novel pyrimidine derivatives as potential anticancer agents

Abbass

Khalil

El‐Naggar

2020

Journal of Heterocyclic Chem

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Herein, a rapid and highly efficient method for the synthesis of a new series of pyrimidine derivatives was demonstrated. The strategy was emanated from the reaction of hydrazinyl pyrimidine derivative (1) with different electrophilic species such as ethyl acetoacetate, ethyl 4,4,4‐trifluoro acetoacetate, and phenyl isothiocyanate following cyclocondensation mechanism to afford the corresponding derivatives (2‐6). Furthermore, condensation of hydrazine derivative (1) with different carbonyl compounds via conventional heating and microwave irradiation conditions was employed as a source of Schiff base derivatives bearing pyrimidine moiety (7‐12). The structural features of all newly synthesized compounds were characterized by elemental and spectroscopic evidences. Some of the synthesized compounds were evaluated for in vitro cytotoxicity. The preliminary screening results showed that most of the tested compounds have moderate cytotoxic activity against HepG2 and HCT‐116 cell lines. Finally, a molecular docking study was conducted to reveal the probable interaction with the thymidylate synthase enzyme.

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“…In continuation for our previous work of design and synthesis of new anticancer agents, [35][36][37][38][39][40][41][42][43][44][45] the main target of this work was the synthesis of new thiazol-5(4H)-ones having the same essential pharmacophoric features of the reported CBSIs (Fig. 5).…”

Section: Rational Drug Designmentioning

confidence: 95%

Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5(4H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site

et al. 2020

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Synthesis, characterization and molecular docking studies of thiouracil derivatives as potent thymidylate synthase inhibitors and potential anticancer agents

Cited by 57 publications

References 37 publications

Design and discovery of new 1,2,4‐triazolo[4,3‐c]quinazolines as potential DNA intercalators and topoisomerase II inhibitors

Design and discovery of new 1,2,4‐triazolo[4,3‐c]quinazolines as potential DNA intercalators and topoisomerase II inhibitors

Eco‐friendly synthesis of novel pyrimidine derivatives as potential anticancer agents

Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5(4H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site

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