Evaluation of synthetic acridones and 4-quinolinones as potent inhibitors of cathepsins L and V

Marques, Emerson Finco; Bueno, Mauro Alves; Duarte, Patrícia; Silva, Larissa R.S.P.; Martinelli, Ariani M.; Santos, Caio Y. dos; Severino, Richele P.; Brὂmme, Dieter; Vieira, Paulo C.; Corrêa, Arlene G.

doi:10.1016/j.ejmech.2012.04.002

Cited by 33 publications

(10 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, SAR and computational studies highlighted acridone 7 as a lead compound for designing synthetic competitive inhibitors of cathepsin V, as it has been reported recently by the same research group [84]. In addition to the polar contacts, nonpolar interactions contribute to the orientation of 7 in the cathepsin V binding site.…”

Section: Acridones As Cathepsin V Inhibitorssupporting

confidence: 58%

Natural Products as Cathepsin Inhibitors

Vidal‐Albalat

González

2016

Studies in Natural Products Chemistry

View full text Add to dashboard Cite

Section: Acridones As Cathepsin V Inhibitorssupporting

confidence: 58%

Natural Products as Cathepsin Inhibitors

Vidal‐Albalat

González

2016

Studies in Natural Products Chemistry

View full text Add to dashboard Cite

“…Petroleum ether, chloroform, ethyl acetate and aqueous extracts of both Ruta, very likely, does not contain secondary metabolites with antimicrobial power, like phenolic oligomers, alkaloids (especially quinolines and acridones) [50][51][52], furoquinolines [48], sterols/ tri-terpenes, rutin, and the low content of coumarins compared to methanolic and ethanolic extracts. Indeed, most of the active antimicrobial compounds identified are apolar and insoluble in water [53].…”

Section: Recently Abts Analysis Of Ethanol Extract Reveals An Ic50mentioning

confidence: 99%

"Evaluation of the Phenolic Contents, Antioxidant and Antimicrobial Activities of Leaves Extracts of Ruta Graveolens"

Halouani¹,

Abdelli²,

Slama³

et al. 2021

BJSTR

View full text Add to dashboard Cite

Ruta graveolens, better known as rue, is a polyvalent herb rich in secondary metabolites that has demonstrated different biological properties and its various medicinal properties. Ruta belongs to the Rutaceae family and is native to the Mediterranean region. We choose same species plant, from two origin, North Africa (Tunisia) and South Europe (France). Different extracts were obtained from dried leaves by using five solvents with increasing polarity, petroleum ether, chloroform, ethyl acetate, ethanol, methanol, and water. Different extracts from both plants, demonstrated in most of tests the same profile. Starting with yield extraction evaluation, a high yields were obtained with ethanol, methanol and aqueous plant extracts. Phenols content assessment reveals an important amount in ethanolic and methanolic extracts of polyphenols, flavonoids and in petroleum ether, chloroform and ethyl acetate of tannins. The antioxidant power was evaluated by using four methods, mainly DPPH, ABTS, β-Carotene and FRAP. Results are expressed as Inhibitory Concentration 50 and the best performance was noted with ethanolic and methanolic extracts.Effect of five organic and aqueous extracts of both plants on growth of two Gramnegative and two Gram-positive bacteria and Candida albicans was evaluated by MIC and MBC determination. Ethanol and methanol extracts of both Ruta exerts a bactericidal effect on different bacterial strain. While, a selective antifungal activity was noted only with methanolic extracts. Results were confirmed with MBC/MIC ratio (less than or equal to 4). Phenols content, especially polyphenols and flavonoids, showed good correlation with antioxidant and antimicrobial activities, which confirm its significant contribution to those activities of Ruta graveolens extracts.

show abstract

“…Acridones are an important class of heterocyclic compounds possessing various biological activities including anticancer 20 , antiherpes, antimalarial 21 , antileishmania 22 , and antibacterial 23 . Synthetic and naturally occurring acridones have been extensively investigated for their inhibitory effects against cathepsin 24,25 , kinases 26 , topoisomerase 27 , surviving 28 , acetylcholinesterase 29 , etc. In addition, acridones have been evaluated as modulators of P-gp mediated multidrug resistance 20 and immunosuppressive agents 30 .…”

Section: Introductionmentioning

confidence: 99%

Probing the Inhibition of Microtubule Affinity Regulating Kinase 4 by N-Substituted Acridones

Voura

Khan

Thysiadis

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Microtubule affinity regulating kinase 4 (MARK4) becomes a unique anti-cancer drug target as its overexpression is responsible for different types of cancers. In quest of novel, effective MARK4 inhibitors, some acridone derivatives were synthesized, characterized and evaluated for inhibitory activity against human MARK4. Among all the synthesized compounds, three (7b, 7d and 7f) were found to have better binding affinity and enzyme inhibition activity in µM range as shown by fluorescence binding, ITC and kinase assays. Here we used functional assays of selected potential lead molecules with commercially available panel of 26 kinases of same family. A distinctive kinase selectivity profile was observed for each compound. The selective compounds were identified with submicromolar cellular activity against MARK4. Furthermore, in vitro antitumor evaluation against cancerous cells (MCF-7 and HepG2) revealed that compounds 7b, 7d and 7f inhibit cell proliferation and predominantly induce apoptosis in MCF-7 cells, with IC50 values of 5.2 ± 1.2 μM, 6.3 ± 1.2 μM, and 5.8 ± 1.4 μM respectively. In addition, these compounds significantly upsurge the oxidative stress in cancerous cells. Our observations support our approach for the synthesis of effective inhibitors against MARK4 that can be taken forward for the development of novel anticancer molecules targeting MARK4.

show abstract

Evaluation of synthetic acridones and 4-quinolinones as potent inhibitors of cathepsins L and V

Cited by 33 publications

References 68 publications

Natural Products as Cathepsin Inhibitors

Natural Products as Cathepsin Inhibitors

"Evaluation of the Phenolic Contents, Antioxidant and Antimicrobial Activities of Leaves Extracts of Ruta Graveolens"

Probing the Inhibition of Microtubule Affinity Regulating Kinase 4 by N-Substituted Acridones

Contact Info

Product

Resources

About