883541-16-0Relevant articles and documents
Design, synthesis and biological evaluation of matrine derivatives as potential anticancer agents
Li, Zheng,Luo, Mengyang,Cai, Bin,Wu, Lichuan,Huang, Mengtian,Haroon-Ur-Rashid,Jiang, Jun,Wang, Lisheng
supporting information, p. 677 - 683 (2018/02/06)
Using matrine (1) as the lead compound, a series of new 14-(N-substituted-2-pyrrolemethylene) matrine and 14-(N-substituted-indolemethylene) matrine derivatives was designed and synthesized for their potential application as anticancer agents. The structure of these compounds was characterized by 1H NMR, 13C NMR and ESI-MS spectral analyses. The target compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (SMMC-7721, A549 and CNE2). The results revealed that compound A6 and B21 displayed the most significant anticancer activity against three cancer cell lines with IC50 values in range of 3.42–8.05 μM, which showed better activity than the parent compound (Matrine) and positive control Cisplatin. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound A6 and B21 could significantly induce the apoptosis of SMMC-7721 and CNE2 cells in a dose-dependent manner. The cell cycle analysis also revealed that compound A6 could cause cell cycle arrest of SMMC-7721 and CNE2 cells at G2/M phase.
Rational modification of semaxanib and sunitinib for developing a tumor growth inhibitor targeting ATP binding site of tyrosine kinase
Kaur, Jagroop,Kaur, Baljit,Singh, Palwinder
supporting information, p. 129 - 133 (2017/12/08)
Analysis of the crystal structure of tyrosine kinase in complexation with an ATP analogue, supplemented with the molecular docking studies of semaxanib and sunitinib in the ATP binding site of the enzyme enabled us to make design of a series of tyrosine k
Structure-activity relationship of pyrrolyl diketo acid derivatives as dual inhibitors of HIV-1 integrase and reverse transcriptase ribonuclease H domain
Cuzzucoli Crucitti, Giuliana,Métifiot, Mathieu,Pescatori, Luca,Messore, Antonella,Madia, Valentina Noemi,Pupo, Giovanni,Saccoliti, Francesco,Scipione, Luigi,Tortorella, Silvano,Esposito, Francesca,Corona, Angela,Cadeddu, Marta,Marchand, Christophe,Pommier, Yves,Tramontano, Enzo,Costi, Roberta,Di Santo, Roberto
, p. 1915 - 1928 (2015/04/27)
The development of HIV-1 dual inhibitors is a highly innovative approach aimed at reducing drug toxic side effects as well as therapeutic costs. HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) are both selective targets
6-(1-benzyl-1 h -pyrrol-2-yl)-2,4-dioxo-5-hexenoic acids as dual inhibitors of recombinant HIV-1 integrase and ribonuclease H, synthesized by a parallel synthesis approach
Costi, Roberta,Métifiot, Mathieu,Esposito, Francesca,Cuzzucoli Crucitti, Giuliana,Pescatori, Luca,Messore, Antonella,Scipione, Luigi,Tortorella, Silvano,Zinzula, Luca,Novellino, Ettore,Pommier, Yves,Tramontano, Enzo,Marchand, Christophe,Di Santo, Roberto
, p. 8588 - 8598 (2013/12/04)
The increasing efficiency of HAART has helped to transform HIV/AIDS into a chronic disease. Still, resistance and drug-drug interactions warrant the development of new anti-HIV agents. We previously discovered hit 6, active against HIV-1 replication and targeting RNase H in vitro. Because of its diketo-acid moiety, we speculated that this chemotype could serve to develop dual inhibitors of both RNase H and integrase. Here, we describe a new series of 1-benzyl-pyrrolyl diketohexenoic derivatives, 7a-y and 8a-y, synthesized following a parallel solution-phase approach. Those 50 analogues have been tested on recombinant enzymes (RNase H and integrase) and in cell-based assays. Approximately half (22) exibited inhibition of HIV replication. Compounds 7b, 7u, and 8g were the most active against the RNase H activity of reverse-transcriptase, with IC50 values of 3, 3, and 2.5 μM, respectively. Compound 8g was also the most potent integrase inhibitor with an IC50 value of 26 nM.
Diketo acids derivatives as dual inhibitors of human immunodeficiency virus type 1 integrase and the reverse transcriptase RNase H Domain
Santo, R. Di
scheme or table, p. 3335 - 3342 (2012/06/18)
The HIV-1 integrase (IN) and reverse transcriptase (RT) are essential enzymes in the virus cycle. RT is crucial for the retrotranscription of the RNA viral genome, while IN is involved in the insertion in host chromosome of the proviral double strand DNA produced by RT. This enzyme has two associated functions: the RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the ribonuclease H (RNase H). The RNase H function catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate. Since the discovery that catalytic cores of both HIV-1 RNase H and IN are folded in a very similar way, have very similar active site geometries, and show the same DDE triad absolutely required for catalytic activity, some researches were devoted to study IN and RNase H dual inhibitor. Our decennial interest in design and synthesis of IN inhibitors led us to study the activity of our compounds also on RNase H activity. The results of the activities showed by pyrrolyl and quinolonyl diketo acids are reported and discussed.
Design, synthesis and biological evaluation of heteroaryl diketohexenoic and diketobutanoic acids as HIV-1 integrase inhibitors endowed with antiretroviral activity
Di Santo,Costi,Artico,Ragno,Greco,Novellino,Marchand,Pommier
, p. 409 - 417 (2007/10/03)
Highly active anti-retroviral therapy (HAART) using reverse transcriptase (RT) and protease (PR) inhibitors and, more recently, inhibitors of the fusion is currently the best clinical approach in combating acquired immunodeficiency syndrome (AIDS), caused
6-Aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays
Costi, Roberta,Di Santo, Roberto,Artico, Marino,Roux, Alessandra,Ragno, Rino,Massa, Silvio,Tramontano, Enzo,La Colla, Massimiliano,Loddo, Roberta,Marongiu, M. Elena,Pani, Alessandra,La Colla, Paolo
, p. 1745 - 1749 (2007/10/03)
A series of 6-aryl-2,4-dioxo-5-hexenoic acids, were synthesized and tested against HIV-1 in cell-based assays and against recombinant HIV-1 integrase (rIN) in enzyme assays. Compound 8a showed potent antiretroviral activity (EC 50=1.5 μM) and s
