Synthesis and characterization of new phthalhydrazothiazole derivatives: A preliminary investigation on their activity against hepatocellular carcinoma

Cardia, Maria Cristina; Distinto, Simona; Maccioni, Elias; Plumitallo, Antonio; Sanna, Laura; Sanna, Maria Luisa; Vigo, S.

doi:10.1002/jhet.138

Cited by 9 publications

(2 citation statements)

References 45 publications

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“…For example, phthalazin-1,4-diones have been reported as potent type II IMP dehydrogenase inhibitors 1 and as active anti-proliferative agents against various human and murine tumor cells, 2,3 particularly hepatocellular carcinoma. 4 In addition, a series of 4-substituted-2 H -phthalazin-1-ones has been studied as potent orally bioavailable poly ADP ribose polymerase (PARP) inhibitors. 5–7 Olaparib (1), MRU-868 (2) and KU0058958 (3) are the most interesting PARP inhibitors based on the 4-substituted-2 H -phthalazin-1-one scaffold ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking, pro-apoptotic, and enzyme inhibition profile

et al. 2020

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Background and aim: The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives. Methods: The synthetic reactions were carried out under both conventional and ultrasonic irradiation conditions. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. In addition to molecular docking studies, the possible mechanism(s) of action were also explored. Results: In general, an improvement in synthetic rates and yields was observed when reactions were carried out under sonication compared with classical conditions. The structures of the products were established based on analytical and spectral data. Derivatives 2e and 7d, in addition to compound 1, had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. These derivatives arrested the cell cycle progression and/or induced apoptosis. This has been manifested by the elevation in the expression of p53 and caspase 3, down-regulation of cdk1, and a reduction in the concentrations of MAPK and Topo II at submicromolar concentrations. The latter results confirmed the molecular docking study. Conclusions: Compound 1 had the best profile on the gene and protein levels (arresting cell cycle and inducing apoptosis). The ability of compounds 1 and 2e to inhibit both MAPK and Topo II nominates these derivatives as potential candidates for further anticancer and antitumor studies. Fig. 2 Structure of the lead anticancer phthalazin-1(2H)-one derivatives 1-3. Scheme 1 General procedure for synthesis of target compounds (2a-e, 3, 4a-d). 3676 | RSC Adv., 2020, 10, 3675-3688 This journal is a Signicant difference (p < 0.05) as compared to untreated cells. The data are expressed as mean AE SEM for two independent experiments. 3678 | RSC Adv., 2020, 10, 3675-3688 This journal is

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Section: Introductionmentioning

confidence: 99%

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking, pro-apoptotic, and enzyme inhibition profile

et al. 2020

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“…There are only two naturally occurring phthalazine derivatives, namely azamerone ( I , Figure 1 ), which was isolated in 2006 from amarine-derived Streptomyces species [ 1 ], and 6-azidotetrazolo[5,1- a ]phthalazine ( II , Figure 1 ), which was isolated in 1985 from Gymnodiniumbreve , a toxic red-tide dinoflagellate [ 2 ]. Some phthalazine derivatives have been reported to possess anticonvulsant [ 3 ], antitumor [ 4 , 5 , 6 ], anti-inflammatory [ 7 ], and antidiabetic and vasorelaxant activities [ 8 ]. Phthalazines have also shown interesting vasodialatory and antihypertensive properties [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

An Efficient Synthesis of Novel Bioactive Thiazolyl-Phthalazinediones under Ultrasound Irradiation

et al. 2017

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Novel 2-thiazolylphthalazine derivatives were efficiently synthesized under ultrasound irradiation, resulting in high yields and short reaction times after optimization of the reaction conditions. All prepared compounds were fully characterized using spectroscopic methods. They were screened for their antimicrobial activity against Gram-positive and Gram-negative bacteria as well as for antifungal activity. The antimicrobial activity profile of the tested compounds showed some promising results. The potent activity of compounds 4d, 7b (117% zone inhibition) and 7c (105% zone inhibition) against Salmonella sp., exceeding that of the reference drug Gentamycin is particularly noteworthy. In general, the newly synthesized thiazolylphthalazine derivatives showed higher antimicrobial activity against the tested Gram-negative bacteria than against Gram-positive bacteria and fungi.

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ChemInform Abstract: Synthesis and Characterization of New Phthalhydrazothiazole Derivatives: A Preliminary Investigation on Their Activity Against Hepatocellular Carcinoma.

et al. 2009

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A straightforward and efficient synthesis of compounds containing both a thiazole and phthalazine moiety is described. Some of these compounds, especially derivative (VIId), show encouraging activity towards liver tumor cells. -(CARDIA*, M. C.; DISTINTO, S.; MACCIONI, E.; PLUMITALLO, A.; SANNA, L.; SANNA, M. L.; VIGO, S.; J. Heterocycl. Chem. 46 (2009) 4, 674-679; Dip. Farm. Chim. Tecnol., Univ. Cagliari, I-09124 Cagliari, Italy; Eng.) -R. Staver 49-163

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Synthesis and characterization of new phthalhydrazothiazole derivatives: A preliminary investigation on their activity against hepatocellular carcinoma

Cited by 9 publications

References 45 publications

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking, pro-apoptotic, and enzyme inhibition profile

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking, pro-apoptotic, and enzyme inhibition profile

An Efficient Synthesis of Novel Bioactive Thiazolyl-Phthalazinediones under Ultrasound Irradiation

ChemInform Abstract: Synthesis and Characterization of New Phthalhydrazothiazole Derivatives: A Preliminary Investigation on Their Activity Against Hepatocellular Carcinoma.

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