• Je něco špatně v tomto záznamu ?

An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors

M. Vettorazzi, E. Angelina, S. Lima, T. Gonec, J. Otevrel, P. Marvanova, T. Padrtova, P. Mokry, P. Bobal, LM. Acosta, A. Palma, J. Cobo, J. Bobalova, J. Csollei, I. Malik, S. Alvarez, S. Spiegel, J. Jampilek, RD. Enriz,

. 2017 ; 139 (-) : 461-481. [pub] 20170810

Jazyk angličtina Země Francie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc18016414

Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b]pyrimido[5,4-f]azepine and two alkyl{3-/4-[1-hydroxy-2-(4-arylpiperazin-1-yl)ethyl]phenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18016414
003      
CZ-PrNML
005      
20180521101539.0
007      
ta
008      
180515s2017 fr f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.ejmech.2017.08.017 $2 doi
035    __
$a (PubMed)28822281
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a fr
100    1_
$a Vettorazzi, Marcela $u Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Instituto Multidisciplinario de Investigaciones Biológicas (IMIBIO-SL), Chacabuco 915, 5700 San Luis, Argentina.
245    13
$a An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors / $c M. Vettorazzi, E. Angelina, S. Lima, T. Gonec, J. Otevrel, P. Marvanova, T. Padrtova, P. Mokry, P. Bobal, LM. Acosta, A. Palma, J. Cobo, J. Bobalova, J. Csollei, I. Malik, S. Alvarez, S. Spiegel, J. Jampilek, RD. Enriz,
520    9_
$a Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b]pyrimido[5,4-f]azepine and two alkyl{3-/4-[1-hydroxy-2-(4-arylpiperazin-1-yl)ethyl]phenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands.
650    _2
$a vztah mezi dávkou a účinkem léčiva $7 D004305
650    _2
$a molekulární modely $7 D008958
650    _2
$a molekulární struktura $7 D015394
650    _2
$a fosfotransferasy s alkoholovou skupinou jako akceptorem $x antagonisté a inhibitory $x metabolismus $7 D017853
650    _2
$a inhibitory proteinkinas $x chemická syntéza $x chemie $x farmakologie $7 D047428
650    _2
$a kvantová teorie $7 D011789
650    _2
$a vztahy mezi strukturou a aktivitou $7 D013329
655    _2
$a časopisecké články $7 D016428
700    1_
$a Angelina, Emilio $u Laboratorio de Estructura Molecular y Propiedades, Área de Química Física, Departamento de Química, Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Avda. Libertad 5460, 3400 Corrientes, Argentina.
700    1_
$a Lima, Santiago $u Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298 USA.
700    1_
$a Gonec, Tomas $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1, 612 42 Brno, Czech Republic.
700    1_
$a Otevrel, Jan $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1, 612 42 Brno, Czech Republic.
700    1_
$a Marvanova, Pavlina $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1, 612 42 Brno, Czech Republic.
700    1_
$a Padrtova, Tereza $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1, 612 42 Brno, Czech Republic.
700    1_
$a Mokry, Petr $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1, 612 42 Brno, Czech Republic.
700    1_
$a Bobal, Pavel $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1, 612 42 Brno, Czech Republic.
700    1_
$a Acosta, Lina M $u Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, Carrera 27, Calle 9, A.A 678, Bucaramanga, Colombia.
700    1_
$a Palma, Alirio $u Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, Carrera 27, Calle 9, A.A 678, Bucaramanga, Colombia.
700    1_
$a Cobo, Justo $u Inorganic and Organic Department, University of Jaén, Campus Las Lagunillas s/n, 23071, Jaén, Spain.
700    1_
$a Bobalova, Janette $u Institute of Analytical Chemistry of the Czech Academy of Sciences, v. v. i., Veveri 97, 602 00 Brno, Czech Republic.
700    1_
$a Csollei, Jozef $u Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1, 612 42 Brno, Czech Republic; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia.
700    1_
$a Malik, Ivan $u Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia.
700    1_
$a Alvarez, Sergio $u Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Instituto Multidisciplinario de Investigaciones Biológicas (IMIBIO-SL), Chacabuco 915, 5700 San Luis, Argentina.
700    1_
$a Spiegel, Sarah $u Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298 USA.
700    1_
$a Jampilek, Josef $u Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia.
700    1_
$a Enriz, Ricardo D $u Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Instituto Multidisciplinario de Investigaciones Biológicas (IMIBIO-SL), Chacabuco 915, 5700 San Luis, Argentina. Electronic address: denriz@unsl.edu.ar.
773    0_
$w MED00001628 $t European journal of medicinal chemistry $x 1768-3254 $g Roč. 139, č. - (2017), s. 461-481
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28822281 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20180515 $b ABA008
991    __
$a 20180521101721 $b ABA008
999    __
$a ok $b bmc $g 1300038 $s 1013254
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 139 $c - $d 461-481 $e 20170810 $i 1768-3254 $m European journal of medicinal chemistry $n Eur J Med Chem $x MED00001628
LZP    __
$a Pubmed-20180515

Najít záznam

Citační ukazatele

    Možnosti archivace