- Design, synthesis, and anticancer screening for repurposed pyrazolo[3,4-d]pyrimidine derivatives on four mammalian cancer cell lines
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The present study reports the synthesis of new purine bioisosteres comprising a pyra-zolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC50 values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopy-rimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.
- Anany, Mohamed A.,Bekhit, Amany A.,Dandekar, Thomas,Othman, Eman M.,Ragab, Hanan M.,Wahid, Ahmed
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- Synthesis method of pyrazolopyrimidine compounds
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The invention relates to a synthesis method of pyrazolopyrimidine compounds. On the basis of the prior art, sodium iodide or potassium iodide is introduced to a hydrazinolysis reaction, the yield andthe purity are increased through the hydrazinolysis step, and accordingly, the total yield is increased. The method has the advantages of mild reaction conditions, high reaction yield and purity, lowproduction cost and the like, and is suitable for production on an industrialization scale.
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- Preparation method of pyrazolopyrimidine compound intermediate
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The invention relates to medicine intermediates and especially provides a synthesis method of a pyrazolopyrimidine hydrazine compound. On the basis of the prior art, NaI or KI is added during a hydrazinolysis reaction, so that yield and purity in the hydrazinolysis reaction are increased. The method has gentle reaction conditions, high reaction yield and product purity, is low in production cost,and is suitable for industrial large-scale production.
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Paragraph 0053-0055
(2018/03/24)
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- 4-Substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives: Design, synthesis, antitumor and EGFR tyrosine kinase inhibitory activity
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Four series of some 4-substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives 5a-f, 6a-f, 8a-f, and 9a-f were designed to be screened for their antitumor activity. All compounds were evaluated against breast (MCF-7) and lung (A-549) cell lines. Six compounds 5a, 5b, 6b, 6e, 9e, and 9f displaying activity against both cell lines were further estimated for their EGFR-TK inhibitory activity where they revealed 41-91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP-binding site of EGFR-TK demonstrated their binding mode where H-bonding interaction with Met793 through N1 of pyrimidine or N2 of pyrazole was observed. Four series of compounds comprising the pyrazolo[3,4-d]pyrimidine core substituted at position 4 with various heterocyclic substitutions were synthesized. Antitumor activity and EGFR-TK inhibition were evaluated.
- Abbas, Safinaz E.-S.,Aly, Enayat I.,Awadallah, Fadi M.,Mahmoud, Walaa R.
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p. 608 - 622
(2015/04/22)
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- Synthesis and biological evaluation of some novel fused pyrazolopyrimidines as potential anticancer and antimicrobial agents
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Synthesis and evaluation of anticancer and antimicrobial activity of some novel pyrazolopyrimidines and fused pyrazolopyrimidines are reported. Twelve analogs were selected to be evaluated for their in vitro anticancer potential against a panel of three h
- Abd El Razik, Heba A.,Abdel Wahab, Abeer E.
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experimental part
p. 184 - 196
(2011/10/07)
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- Synthesis of new sulfur-linked 1,2,4-triazolothienopyrimidine and 1,2,4-triazolopyrazolopyrimidine derivatives containing fused heterocyclic pyrimidines
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(Chemical Equation Presented) A series of novel bis-heterocyclic compounds 12-20 were synthesized by integrating fused heterocyclic pyrimidines, such as thienopyrimidine and pyrazolopyrimidine into the scaffold of thienotriazolopyrimidines, and pyrazolotriazolopyrimidines through a sulfur-linkage.
- Song, Yang-Heon,Son, Hoon Young
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scheme or table
p. 1183 - 1187
(2010/11/16)
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- Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors
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A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Ar1) determined this to be a tight binding region with little room for modification. As predicted from the model, a large variety of modifications could be incorporated into the hydrazone aryl ring. This work led to GSK-3 inhibitors in the low nano-molar range.
- Peat, Andrew J.,Boucheron, Joyce A.,Dickerson, Scott H.,Garrido, Dulce,Mills, Wendy,Peckham, Jennifer,Preugschat, Frank,Smalley, Terrence,Schweiker, Stephanie L.,Wilson, Jayme R.,Wang, Tony Y.,Zhou, Huiqiang Q.,Thomson, Stephen A.
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p. 2121 - 2125
(2007/10/03)
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