Studies on quinones. Part 41: Synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones☆

Valderrama, Jaime A.; González, Marcelo; Pessoa‐Mahana, C. David; Tapia, Ricardo A.; Fillion, H.; Pautet, F.; Rodrı́guez, Jaime A.; Theoduloz, Cristina; Schmeda-Hirschmann, Guillermo

doi:10.1016/j.bmc.2006.03.008

Cited by 33 publications

(23 citation statements)

References 26 publications

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“…8 ± 11, 31, 33 ± 37 The C = C double bond of the 1-azadiene system of hydrazone may form a part of a carbocyclic moiety or a heterocycle. 8,33,45,61,62 Thus, reaction between cyclohex-1enecarbaldehyde hydrazone (21) and 2-bromo-8-hydroxynaphthalene-1,4-dione is used to obtain angular tetracyclic quinones 22 (Scheme 10). 45 …”

Section: Methodsmentioning

confidence: 99%

Hydrazones as substrates for cycloaddition reactions

Belskaya¹,

Eliseeva²,

Бакулев³

2015

Russ. Chem. Rev.

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Section: Methodsmentioning

confidence: 99%

Hydrazones as substrates for cycloaddition reactions

Belskaya¹,

Eliseeva²,

Бакулев³

2015

Russ. Chem. Rev.

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“…Some are endowed with antitumor or antifungal properties [30]. On the other hand, some pyridine and isoquinoline derivatives have various biological properties such as antimicrobial [31], anticancer [32-35] activities.…”

Section: Introductionmentioning

confidence: 99%

Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1,3-dihydropyridine, chromene and chromenopyridine moieties

Alsaid

Ghorab

Nissan

2012

Chemistry Central Journal

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Several new sulfonebiscompounds having a biologically active 1,2-dihydropyridine-2-one 3–19, acrylamide 20, chromene 21, 22 and chromenopyridine 23, 24 moieties were synthesized and evaluated as potential anticancer agents. The structures of the products were confirmed via elemental analyses and spectral data. The screening tests showed that many of the biscompounds obtained exhibited good anticancer activity against human breast cell line (MCF7) comparable to doxorubicin which was used as reference drug. Compounds 11, 17 and 24 showed IC50 values 35.40 μM, 29.86 μM and 30.99 μM, respectively. In order to elucidate the mechanism of action of the synthesized compounds as anticancer agents, docking on the active site of farnesyltransferase and arginine methyltransferase was also performed and good results were obtained.

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“…Our group has recently synthesized and characterized the in vitro antitumor capacity of several polycyclic quinones (13)(14)(15)(16)(17)(18). These molecules may represent an interesting therapeutic tool.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of human topoisomerase I and activation of caspase-3 by aza-angucyclinones and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones

et al. 2012

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Abstract.Cancer is the second cause of death in the world after cardiovascular diseases. Cancer cells acquire capacities not present in normal cells, such as self-sufficiency, resistance to antiproliferative stimuli, evasion of apoptosis, unlimited replication, invasiveness and metastasis. Consequently, it is of major interest to explore and develop molecules with anticancer activity directed to specific targets. In this study, we aimed to evaluate two series of polycyclic quinones: aza-angucyclinone and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones, in their capacity to inhibit human topoisomerase I (TOP1) and to trigger apoptosis through activation of caspase-3. We evaluated the capacity of the two series of polycyclic quinones to inhibit TOP1, using a DNA supercoiled relaxation assay and their capacity to induce apoptosis through the activation of caspase-3 in HL60 cells. Both series of quinones inhibited TOP1 activity over 50%. When we evaluated the pro-apoptotic capacity of both series of quinones, at therapeutically relevant concentrations, the arylaminoquinones ADPA-1CC (methyl 7-(4-methoxyphenyl)amino-1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate), P4 (9-phenylamino-3,4-dihydrophenanthridine-1,7,10(2H)-trione) and the aza-angucyclinone OH-6H (8-hydroxy-2,4-dimethyl-2H,4H-benzo[g]pyrimido [4,5-c]isoquinoline-1,3,7,12-tetraone) increased the caspase-3 activity by approximately 2-fold over the control. The series of the arylaminoquinones and aza-angucyclinones showed differential antiproliferative capacity. We further identified a group of them that showed antiproliferative capacity possibly through inhibition of TOP1 and by activation of caspase-3. This group of molecules may represent a potential pharmacological tool in the treatment against cancer.

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Studies on quinones. Part 41: Synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones☆

Cited by 33 publications

References 26 publications

Hydrazones as substrates for cycloaddition reactions

Hydrazones as substrates for cycloaddition reactions

Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1,3-dihydropyridine, chromene and chromenopyridine moieties

Inhibition of human topoisomerase I and activation of caspase-3 by aza-angucyclinones and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones

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