Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents.

Antineoplastic Agents / chemistry Apoptosis / drug effects Binding Sites Carbonic Anhydrase IX / chemistry Carbonic Anhydrase Inhibitors / chemistry Catalytic Domain Cell Cycle / drug effects Cell Line, Tumor Humans Hydrophobic and Hydrophilic Interactions Isatin / chemistry Molecular Docking Simulation Phenylurea Compounds / pharmacology Protein Binding Sulfonamides / pharmacology Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
Anticancer activity SLC-0111 hybrids Selective hCA IX and XII inhibitors Tail approach VEGFR-2 inhibitors

Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
15 Jan 2019
Historique:
received: 25 09 2018
revised: 11 10 2018
accepted: 31 10 2018
pubmed: 18 11 2018
medline: 5 2 2019
entrez: 17 11 2018
Statut: ppublish

Résumé

Herein we report the design and synthesis of novel N-substituted isatins-SLC-0111 hybrids (6a-f and 9a-l). A structural extension approach was adopted via N-alkylation and N-benzylation of isatin moiety to enhance the tail hydrophobic interactions within the carbonic anhydrase (CA) IX active site. Thereafter, a hybrid pharmacophore approach was utilized via merging the pharmacophoric elements of isatin and SLC-0111 in a single chemical framework. As planned, a substantial improvement of inhibitory profile of the target hybrids (K

Identifiants

DOI: 10.1016/j.ejmech.2018.10.068 PMID: 30445264
pubmed: 30445264
pii: S0223-5234(18)30946-2
doi: 10.1016/j.ejmech.2018.10.068
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Carbonic Anhydrase Inhibitors 0
Phenylurea Compounds 0
SLC-0111 0
Sulfonamides 0
Isatin 82X95S7M06
KDR protein, human EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-2 EC 2.7.10.1
Carbonic Anhydrase IX EC 4.2.1.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

147-160

Informations de copyright

Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Auteurs

Wagdy M Eldehna (WM)

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt. Electronic address: wagdy2000@gmail.com.

Mahmoud F Abo-Ashour (MF)

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt.

Alessio Nocentini (A)

Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.

Radwan S El-Haggar (RS)

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.

Silvia Bua (S)

Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.

Alessandro Bonardi (A)

Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.

Sara T Al-Rashood (ST)

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

Ghada S Hassan (GS)

Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.

Paola Gratteri (P)

Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.

Hatem A Abdel-Aziz (HA)

Department of Applied Organic Chemistry, National Research Center, Dokki, Giza, P.O. Box 12622, Egypt.

Claudiu T Supuran (CT)

Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes néoplasiques › Carbonic anhydrase IX › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de l'anhydrase carbonique › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Domaine catalytique › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Cycle cellulaire › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Phénomènes chimiques › Interactions hydrophobes et hydrophiles › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Indoles › Isatine › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de docking moléculaire › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Phénylurées › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Composés chimiques organiques › Composés du soufre › Sulfones › Sulfonamides › Enhancement of the tail hydrophobic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs aux facteurs de croissance endothéliale vasculaire › Récepteur-2 au facteur croissance endothéliale vasculaire › Enhancement of the tail hydrophobic...