Design and Synthesis of Phthalazine-based Compounds As Potent Anticancer Agents with Potential Antiangiogenic Activity Via VEGFR-2 Inhibition

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2019 Jul 20

PMID 31322015

Citations 7

Authors

Salwa Elmeligie

Asmaa M Aboul-Magd

Deena S Lasheen

Tamer M Ibrahim

Tamer M Abdelghany

Sohair M Khojah

Khaled A M Abouzid

Affiliations

Soon will be listed here.

Abstract

In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds () exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI values ranging from 0.15 to 8.41 µM. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas () with ICs of 4.4, 2.7 and 2.5 μM, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10 μM, respectively. Additionally, compounds ( were found to induce cell cycle arrest at S phase boundary. Compound triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death.

Citing Articles

Synthesis and Structure of Novel Hybrid Compounds Containing Phthalazin-1(2)-imine and 4,5-Dihydro-1-imidazole Cores and Their Sulfonyl Derivatives with Potential Biological Activities.

Balewski L, Gdaniec M, Hering A, Furman C, Ghinet A, Kokoszka J Int J Mol Sci. 2024; 25(21).

PMID: 39519047 PMC: 11546079. DOI: 10.3390/ijms252111495.

Rationale, docking, ADMET profile, design, synthesis and cytotoxicity evaluations of phthalazine derivatives as VEGFR-2 inhibitors and apoptosis inducers.

Bayoumi H, Ibrahim M, Dahab M, Khedr F, El-Adl K RSC Adv. 2024; 14(37):27110-27121.

PMID: 39193307 PMC: 11348385. DOI: 10.1039/d4ra04956j.

Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition.

El Sayed D, El Rayes S, Soliman H, AlBalaa I, Alturki M, Al Khzem A RSC Adv. 2024; 14(19):13027-13043.

PMID: 38660526 PMC: 11040327. DOI: 10.1039/d4ra02103g.

Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents-In Vitro Evaluation against Breast Cancer Cells.

Guillen-Mancina E, Garcia-Lozano M, Burgos-Moron E, Mazzotta S, Martinez-Aguado P, Calderon-Montano J Int J Mol Sci. 2023; 24(23).

PMID: 38069364 PMC: 10706865. DOI: 10.3390/ijms242317041.

Synthesis of phthalazine-based derivatives as selective anti-breast cancer agents through EGFR-mediated apoptosis: in vitro and in silico studies.

Emam S, El Rayes S, Ali I, Soliman H, Nafie M BMC Chem. 2023; 17(1):90.

PMID: 37501139 PMC: 10375784. DOI: 10.1186/s13065-023-00995-2.

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