RT Journal Article
T1 Antitumor Activity of Quinazolinone Alkaloids Inspired by Marine Natural Products
A1 Long, Solida
A1 Resende, Diana I. S. P.
A1 Kijjoa, Anake
A1 Silva, Artur M. S.
A1 Pina, André
A1 Vasconcelos, M. Helena
A1 Sousa, Emília
A1 Pinto, Madalena M. M.
A1 Fernández Marcelo, Tamara
AB Many fungal quinazolinone metabolites, which contain the methyl-indole pyrazino [1,2-b]quinazoline-3,6-dione core, have been found to possess promising antitumor activity. The purpose of this work was to synthesize the enantiomeric pairs of two members of this quinazolinone family, to explore their potential as antitumor and their ability to revert multidrug resistance. The marine natural product fiscalin B (4c), and antienantiomers (4b, 5b, and 5c) were synthesized via a one-pot approach, while the syn enantiomers (4a, 4d, 5a, and 5d) were synthetized by a multi-step procedure. These strategies used anthranilic acid (i), chiral N-protected α-amino acids (ii), and tryptophan methyl esters (iii) to form the core ring of pyrazino[2,1-b]quinazoline-3,6-dione scaffold. Four enantiomeric pairs, with different enantiomeric purities, were obtained with overall yields ranging from 7 to 40%. Compounds 4a–d and 5a–d were evaluated for their growth inhibitory effect against two tumor cell lines. Differences between enantiomeric pairs were noted and 5a–d displayed GI50 values ranging from 31 to 52 μM, which are lower than those of 4a–d. Nevertheless, no effect on P-glycoprotein (P-gp) modulation was observed for all compounds. This study disclosed new data for fiscalin B (4c), as well as for its analogues for a future development of novel anticancer drug leads.
PB MDPI
SN 1660-3397
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/128442
UL https://hdl.handle.net/20.500.14352/128442
LA eng
NO Long S, Resende DISP, Kijjoa A, et al. Antitumor Activity of Quinazolinone Alkaloids Inspired by Marine Natural Products. Marine Drugs 2018;16:261. https://doi.org/10.3390/md16080261
NO Foundation for Science and Technology (Portugal)
NO European Regional Development Fund
DS Docta Complutense
RD 21 ene 2026