Pretražite po imenu i prezimenu autora, mentora, urednika, prevoditelja

Napredna pretraga

Pregled bibliografske jedinice broj: 1085809

Novel Harmicines with Improved Potency against Plasmodium


Marinović, Marina; Perković, Ivana; Fontinha, Diana; Prudêncio, Miguel; Held, Jana; Pessanha de Carvalho, Lais; Tandarić, Tana; Vianello, Robert; Zorc, Branka; Rajić, Zrinka
Novel Harmicines with Improved Potency against Plasmodium // Molecules, 25 (2020), 19; 4376, 19 doi:10.3390/molecules25194376 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 1085809 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Novel Harmicines with Improved Potency against Plasmodium

Autori
Marinović, Marina ; Perković, Ivana ; Fontinha, Diana ; Prudêncio, Miguel ; Held, Jana ; Pessanha de Carvalho, Lais ; Tandarić, Tana ; Vianello, Robert ; Zorc, Branka ; Rajić, Zrinka

Izvornik
Molecules (1420-3049) 25 (2020), 19; 4376, 19

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
harmine ; cinnamic acid ; amide ; antiplasmodial activity ; PfHsp90 ; molecular dynamics simulations ; P. berghei ; P. falciparum

Sažetak
Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1, 2, 3-triazolo [4, 5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N, N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija



POVEZANOST RADA


Projekti:
UIP-2017-05-5160 - Derivati harmina kao potencijalni antimalarici (CLICKforMALARIA) (Rajić Džolić, Zrinka, HRZZ - 2017-05) ( POIROT)

Ustanove:
Farmaceutsko-biokemijski fakultet, Zagreb,
Institut "Ruđer Bošković", Zagreb

Poveznice na cjeloviti tekst rada:

doi www.mdpi.com fulir.irb.hr

Citiraj ovu publikaciju:

Marinović, Marina; Perković, Ivana; Fontinha, Diana; Prudêncio, Miguel; Held, Jana; Pessanha de Carvalho, Lais; Tandarić, Tana; Vianello, Robert; Zorc, Branka; Rajić, Zrinka
Novel Harmicines with Improved Potency against Plasmodium // Molecules, 25 (2020), 19; 4376, 19 doi:10.3390/molecules25194376 (međunarodna recenzija, članak, znanstveni)
Marinović, M., Perković, I., Fontinha, D., Prudêncio, M., Held, J., Pessanha de Carvalho, L., Tandarić, T., Vianello, R., Zorc, B. & Rajić, Z. (2020) Novel Harmicines with Improved Potency against Plasmodium. Molecules, 25 (19), 4376, 19 doi:10.3390/molecules25194376.
@article{article, author = {Marinovi\'{c}, Marina and Perkovi\'{c}, Ivana and Fontinha, Diana and Prud\^{e}ncio, Miguel and Held, Jana and Pessanha de Carvalho, Lais and Tandari\'{c}, Tana and Vianello, Robert and Zorc, Branka and Raji\'{c}, Zrinka}, year = {2020}, pages = {19}, DOI = {10.3390/molecules25194376}, chapter = {4376}, keywords = {harmine, cinnamic acid, amide, antiplasmodial activity, PfHsp90, molecular dynamics simulations, P. berghei, P. falciparum}, journal = {Molecules}, doi = {10.3390/molecules25194376}, volume = {25}, number = {19}, issn = {1420-3049}, title = {Novel Harmicines with Improved Potency against Plasmodium}, keyword = {harmine, cinnamic acid, amide, antiplasmodial activity, PfHsp90, molecular dynamics simulations, P. berghei, P. falciparum}, chapternumber = {4376} }
@article{article, author = {Marinovi\'{c}, Marina and Perkovi\'{c}, Ivana and Fontinha, Diana and Prud\^{e}ncio, Miguel and Held, Jana and Pessanha de Carvalho, Lais and Tandari\'{c}, Tana and Vianello, Robert and Zorc, Branka and Raji\'{c}, Zrinka}, year = {2020}, pages = {19}, DOI = {10.3390/molecules25194376}, chapter = {4376}, keywords = {harmine, cinnamic acid, amide, antiplasmodial activity, PfHsp90, molecular dynamics simulations, P. berghei, P. falciparum}, journal = {Molecules}, doi = {10.3390/molecules25194376}, volume = {25}, number = {19}, issn = {1420-3049}, title = {Novel Harmicines with Improved Potency against Plasmodium}, keyword = {harmine, cinnamic acid, amide, antiplasmodial activity, PfHsp90, molecular dynamics simulations, P. berghei, P. falciparum}, chapternumber = {4376} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Citati:





    Contrast
    Increase Font
    Decrease Font
    Dyslexic Font