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001-es BibID:	BIBFORM056763
Első szerző:	Begum, Jaida
Cím:	Computationally motivated synthesis and enzyme kinetic evaluation of N-([beta]-D-glucopyranosyl)-1,2,4-triazolecarboxamides as glycogen phosphorylase inhibitors / Jaida Begum, Gergely Varga, Tibor Docsa, Pal Gergely, Joseph M. Hayes, Laszló Juhász, Laszló Somsák
Dátum:	2015
ISSN:	2040-2503 2040-2511
Megjegyzések:	Following our recent study of N-(b-D-glucopyranosyl)oxadiazolecarboxamides (Polyák et al., Biorg. Med. Chem. 2013, 21, 5738) revealed as moderate inhibitors of glycogen phosphorylase (GP), in silico docking calculations using Glide have been performed on N-(?-D-glucopyranosyl)-1,2,4-triazolecarboxamides with different aryl substituents predicting more favorable binding at GP. The ligands were subsequently synthesized in moderate yields using N-(2,3,4,6-tetra-O-acetyl-?-D-glucopyranosyl)-tetrazole-5-carboxamide as starting material. Kinetics experiments against rabbit muscle glycogen phosphorylase b (RMGPb) revealed the ligands to be low mM GP inhibitors; the phenyl analogue (Ki =1 mM) is one of the most potent N-(?-D-glucopyranosyl)-heteroaryl-carboxamide-type inhibitors of the GP catalytic site discovered to date. Based on QM and QM/MM calculations, the potency of the ligands is predicted to arise from favorable intra- and intermolecular hydrogen bonds formed by the most stable solution phase tautomeric (t2) state of the 1,2,4-triazole in a conformationally dynamic system. ADMET property predictions revealed the compounds to have promising pharmacokinetic properties without any toxicity. This study highlights the benefits of a computationally led approach to GP inhibitor design.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban Doktori iskola
Megjelenés:	MedChemComm. - 6 : 1 (2015), p. 80-89. -
További szerzők:	Varga Gergely (1982-) (vegyész) Docsa Tibor (1975-) (vegyész, biokémikus) Gergely Pál (1947-) (biokémikus) Hayes, Joseph M. Juhász László (1973-) (vegyész) Somsák László (1954-) (vegyész)
Pályázati támogatás:	77712 OTKA 109450 OTKA TÁMOP-4.2.2-08/1-2008-0014 TÁMOP TÁMOP-4.2.2/B-10/1-2010-0024 TÁMOP Kémiai Tudományok Doktori Iskola BAROSS REG_EA_09-1-2009-0028-LCMS_TAN Egyéb
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001-es BibID:	BIBFORM042457
Első szerző:	Penov-Gaši, Katarina M.
Cím:	Selective antitumour activity and ER[alpha] molecular docking studies of newly synthesized d-homo fused steroidal tetrazoles / Katarina M. Penov-Gaši, Aleksandar M. Oklješa, Edward T. Petri, Andjelka S. Ćelić, Evgenija A. Djurendić, Olivera R. Klisurić, Janos J. Csanadi, Gyula Batta, Andrea R. Nikolić, Dimitar S. Jakimov, Marija N. Sakač
Dátum:	2013
ISSN:	2040-2503 2040-2511
Megjegyzések:	Here we report a convenient "click" synthesis for D-homo fused steroidal tetrazoles 11-14 from androstane and estratriene 16,17-seco-16-nitrile-17-mesyloxy derivatives 5-8, via intramolecular 1,3-dipolar cycloaddition from in situ generated 16,17-seco-17-azido-16-nitriles 5a-8a. Products were validated by 1H/13C-NMR, IR, HRMS, and structurally characterized by X-ray crystallography and computational methods. Compounds were evaluated as potential anti-proliferative agents against a panel of human cancer cell lines. D-Homo fused steroidal tetrazoles 13 and 14 appear to have specific, selective antiproliferative effects against estrogen receptor positive (ER+) breast adenocarcinoma cells, which correlate with binding energies calculated from molecular docking to the estrogen receptor [alpha]-ligand binding domain (ER[alpha]-LBD). Moreover, molecular docking suggests that D-ring fused steroidal tetrazoles 13 and 14 could bind to ER[alpha]-LBD in a manner similar to known anti-estrogenic compounds. Addition of a D-homo fused tetrazole group appears to structurally mimic the hydrogen bonding potential of [beta]-estradiol, suggesting their general utility in designing novel steroidal tetrazole derivatives as antiestrogens or inhibitors of steroidogenic enzymes.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	MedChemComm. - 4 : 2 (2013), p. 317-323. -
További szerzők:	Oklješa, Aleksandar M. Petri, Edward T. Ćelić, Andjelka S. Djurendić, Evgenija A. Klisurić, Olivera R. Csanádi János Batta Gyula (1953-) (molekula-szerkezet kutató) Nikolić, Andrea R. Jakimov, Dimitar S. Sakač, Marija N.
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