Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Novel coumarin-6-sulfonamide-chalcone hybrids as glutathione transferase P1-1 inhibitors

A. Sabt, S. Kitsos, MS. Ebaid, V. Furlan, PD. Pantiora, M. Tsolka, EB. Elkaeed, MF. Hamissa, N. Angelis, OE. Tsitsilonis, AC. Papageorgiou, U. Bren, NE. Labrou

. 2024 ; 19 (8) : e0306124. [pub] 20240814

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24019337

Multidrug resistance (MDR) mechanisms in cancer cells are greatly influenced by glutathione transferase P1-1 (hGSTP1-1). The use of synthetic or natural compounds as hGSTP1-1 inhibitors is considered an effective approach to overcome MDR. Nine compounds consisting of coumarin-6-sulfonamide linked to chalcone derivatives were synthesized and evaluated for their ability to inhibit hGSTP1-1. Among the synthetic derivatives, compounds 5g, 5f, and 5a displayed the most potent inhibitory effect, with IC50 values of 12.2 ± 0.5 μΜ, 12.7 ± 0.7 and 16.3 ± 0.6, respectively. Kinetic inhibition analysis of the most potent molecule, 5g, showed that it behaves as a mixed-type inhibitor of the target enzyme. An in vitro cytotoxicity assessment of 5a, 5f, and 5g against the human prostate cancer cell lines DU-145 and PC3, as well as the breast cancer cell line MCF-7, demonstrated that compound 5g exhibited the most pronounced cytotoxic effect on all tested cell lines. Molecular docking studies were performed to predict the structural and molecular determinants of 5g, 5f, and 5a binding to hGSTP1-1. In agreement with the experimental data, the results revealed that 5g exhibited the lowest docking score among the three studied inhibitors as a consequence of shape complementarity, governed by van der Waals, hydrogen bonds and a π-π stacking interaction. These findings suggest that coumarin-chalcone hybrids offer new perspectives for the development of safe and efficient natural product-based sensitizers that can target hGSTP1-1 for anticancer purposes.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24019337
003      
CZ-PrNML
005      
20241024111446.0
007      
ta
008      
241015s2024 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1371/journal.pone.0306124 $2 doi
035    __
$a (PubMed)39141629
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Sabt, Ahmed $u Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Center, Dokki, Cairo, Egypt $1 https://orcid.org/0000000169760196
245    10
$a Novel coumarin-6-sulfonamide-chalcone hybrids as glutathione transferase P1-1 inhibitors / $c A. Sabt, S. Kitsos, MS. Ebaid, V. Furlan, PD. Pantiora, M. Tsolka, EB. Elkaeed, MF. Hamissa, N. Angelis, OE. Tsitsilonis, AC. Papageorgiou, U. Bren, NE. Labrou
520    9_
$a Multidrug resistance (MDR) mechanisms in cancer cells are greatly influenced by glutathione transferase P1-1 (hGSTP1-1). The use of synthetic or natural compounds as hGSTP1-1 inhibitors is considered an effective approach to overcome MDR. Nine compounds consisting of coumarin-6-sulfonamide linked to chalcone derivatives were synthesized and evaluated for their ability to inhibit hGSTP1-1. Among the synthetic derivatives, compounds 5g, 5f, and 5a displayed the most potent inhibitory effect, with IC50 values of 12.2 ± 0.5 μΜ, 12.7 ± 0.7 and 16.3 ± 0.6, respectively. Kinetic inhibition analysis of the most potent molecule, 5g, showed that it behaves as a mixed-type inhibitor of the target enzyme. An in vitro cytotoxicity assessment of 5a, 5f, and 5g against the human prostate cancer cell lines DU-145 and PC3, as well as the breast cancer cell line MCF-7, demonstrated that compound 5g exhibited the most pronounced cytotoxic effect on all tested cell lines. Molecular docking studies were performed to predict the structural and molecular determinants of 5g, 5f, and 5a binding to hGSTP1-1. In agreement with the experimental data, the results revealed that 5g exhibited the lowest docking score among the three studied inhibitors as a consequence of shape complementarity, governed by van der Waals, hydrogen bonds and a π-π stacking interaction. These findings suggest that coumarin-chalcone hybrids offer new perspectives for the development of safe and efficient natural product-based sensitizers that can target hGSTP1-1 for anticancer purposes.
650    _2
$a lidé $7 D006801
650    12
$a kumariny $x chemie $x farmakologie $7 D003374
650    12
$a simulace molekulového dockingu $7 D062105
650    12
$a glutathion-S-transferasa fí $x antagonisté a inhibitory $x metabolismus $7 D051549
650    12
$a sulfonamidy $x chemie $x farmakologie $7 D013449
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a chalkon $x chemie $x farmakologie $7 D002599
650    _2
$a protinádorové látky $x farmakologie $x chemie $7 D000970
650    _2
$a chalkonoidy $x chemie $x farmakologie $7 D047188
650    _2
$a inhibitory enzymů $x farmakologie $x chemie $7 D004791
650    _2
$a MFC-7 buňky $7 D061986
655    _2
$a časopisecké články $7 D016428
700    1_
$a Kitsos, Stefanos $u Laboratory of Enzyme Technology, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
700    1_
$a Ebaid, Manal S $u Department of Chemistry, College of Science, Northern Border University, Arar, Saudi Arabia
700    1_
$a Furlan, Veronika $u Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia
700    1_
$a Pantiora, Panagiota D $u Laboratory of Enzyme Technology, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
700    1_
$a Tsolka, Magdalini $u Laboratory of Enzyme Technology, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
700    1_
$a Elkaeed, Eslam B $u Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Diriyah, Saudi Arabia
700    1_
$a Hamissa, Mohamed Farouk $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Prague, Czech Republic
700    1_
$a Angelis, Nikolaos $u Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens (NKUA), Athens, Greece
700    1_
$a Tsitsilonis, Ourania E $u Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens (NKUA), Athens, Greece
700    1_
$a Papageorgiou, Anastassios C $u Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
700    1_
$a Bren, Urban $u Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia $u Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Koper, Slovenia $u Institute of Environmental Protection and Sensors, Maribor, Slovenia
700    1_
$a Labrou, Nikolaos E $u Laboratory of Enzyme Technology, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece
773    0_
$w MED00180950 $t PloS one $x 1932-6203 $g Roč. 19, č. 8 (2024), s. e0306124
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39141629 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20241015 $b ABA008
991    __
$a 20241024111439 $b ABA008
999    __
$a ok $b bmc $g 2201902 $s 1231310
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 19 $c 8 $d e0306124 $e 20240814 $i 1932-6203 $m PloS one $n PLoS One $x MED00180950
LZP    __
$a Pubmed-20241015

Find record

Citation metrics

Archiving options