Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives

“…Being a building unit of DNA and RNA, pyrimidine derivatives were found to be associated with a variety of chemotherapeutic effects including antimicrobial [21,22], antitubercular [23], antifungal [24], antiviral [25], and antitumor activities [26,27]. Furthermore, many pyrimidinethiones and their thioether derivatives were proved to exhibit potent anticancer as well as antimicrobial activities [28,29], besides being analogs of S-DABOs (dihydro-alkylthio-benzyl-oxopyrimidines) which possess antiproliferative as well as antiviral activities [30].…”

Section: Introductionmentioning

confidence: 98%

Synthesis of Some Pyrazolines and Pyrimidines Derived from Polymethoxy Chalcones as Anticancer and Antimicrobial Agents

Rostom

Badr

Razik

et al. 2011

Archiv der Pharmazie

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The synthesis of a series of certain polymethoxy chalcones and some derived pyrazole, pyrimidine, and thiazolopyrimidine ring structures is reported. Eleven compounds 4, 6, 9, 11, 14-17, 22, 24, and 25 were selected by the National Cancer Institute (NCI) to be screened for their in-vitro anticancer activity, whereas all the synthesized compounds were evaluated for their in-vitro antimicrobial activity. Compounds 4, 6, and 11 were found to possess a significant broad spectrum antitumor potential against most of the tested subpanel tumor cell lines. The pyrazolines 4 and 6 displayed remarkable growth inhibitory activities (GI(50) MG-MID values of 2.10 and 1.38 µM, respectively), together with moderate cytostatic effects (TGI MG-MID values of 47.9 and 42.7 µM, respectively). Meanwhile, the pyrimidin-2-one 11 showed a noticeable overall tumor growth inhibitory activity, together with high cytostatic and cytotoxic efficacies (GI(50) , TGI and LC(50) MG-MID values of 3.39, 17.4, and 61.7 µM, respectively). On the other hand, compounds 3, 4, 13, 15, 19, 20, and 23 were found to be the most active antimicrobial members in this investigation with a broad spectrum of activity. Compound 23 was four times superior to ampicillin against Pseudomonas aeruginosa. The best antifungal activity was demonstrated by compounds 4, 5, and 11 which possessed almost half the activity of clotrimazole against Candida albicans. Collectively, the obtained biological results suggest that compound 4 could be considered as a possible dual antimicrobial-anticancer agent.

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“…From another point of view, the piperazinyl moiety, the small rigid heterocyclic motif, has been successfully incorporated in several potent kinase inhibitors(L. Garuti, 2009,Shallal& Russu, 2011,Rice et al, 2012,Zhang et al, 2010,Pollard& Mortimore, 2009). The aryl piperazine based derivative (VII) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Phthalazine Based Derivatives as Potential Anticancer Agents

Elmeligie¹

2016

Al-Azhar Journal of Pharmaceutical Sciences

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In an attempt to develop novel targeted anticancer agents, a series of novel substituted phthalazine derivatives has been designed and synthesized as inhibitors of vascular endothelial growth factor receptor (VEGFR) kinase enzyme in accordance to SAR studies of known VEGFR inhibitors. The designed compounds incorporated a biarylamide or biarylurea tail linked to a phthalazine scaffold via an amino or ether linkage or else incorporated an N-substituted piperazine motif at position 1 of the phthalazine core. The prepared compounds were evaluated for their enzymatic inhibition of VEGFR-2 kinase. Furthermore, three of the phthalazines bearing a biarylurea (6b, 6e &7b) exhibited excellent broad spectrum cell growth inhibition against NCI full 60 cell panel with GI 50 values between 0.15-5μM. In addition, docking studies were performed through docking of the investigated compounds into VEGFR-2 binding site in order to gain further insight into their binding affinities and binding interactions with the VEGFR-2 kinase.

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Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives

Cited by 45 publications

References 63 publications

CDK8 kinase—An emerging target in targeted cancer therapy

CDK8 kinase—An emerging target in targeted cancer therapy

Synthesis of Some Pyrazolines and Pyrimidines Derived from Polymethoxy Chalcones as Anticancer and Antimicrobial Agents

Design and Synthesis of Phthalazine Based Derivatives as Potential Anticancer Agents

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