Synthesis and structure elucidation of novel fused 1,2,4-triazine derivatives as potent inhibitors targeting CYP1A1 activity
Artikel i vetenskaplig tidskrift, 2012

Synthesis and structure elucidation of new series of novel fused 1,2,4-triazine derivatives 3a-3f, 4a-4i and 6a-6b and their inhibitory activities are presented. Molecular structures of the synthesized compounds were confirmed by H-1 NMR, C-13 NMR, MS spectra and elemental analyses. X-ray crystallographic analysis was performed on 2-acetyl-8-(N,N-diacetylamino)-6-(4-methoxybenzyl)-3-(4-methoxy-phenyl)- 7-oxo-2,3-dihydro-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazine 3d and 2-acetyl-8-(N-acetyl- amino)-6-benzyl-3-(4-chlorophenyl)-3-methyl-7-oxo-2,3-dihydro-7H-[1,2,4] triazolo[4,3-b][1,2,4]triazine 4e to secure their structures. The inhibitory effect of these compounds toward the CPY1A1 activity was screened to determine their potential as promising anticancer drugs. Our data showed that compounds 4e, 5a, 5b and 6b possess the highest inhibitory effects among all tested compounds. Furthermore, analysis of triazolotriazine derivatives docking showed that these compounds bind only at the interface of substrate recognition site 2 (SRS2) and (SRS6) at the outer surface of the protein. Amino-acids ASN214, SER216 and ILE462 participate in the binding of these compounds through H-bonds.

anti-hiv

agents

Triazinotetrazine

Triazolotriazine

Aryl

anticancer drugs

nitrogen systems bearing

X-ray

enzymes

NMR

antitumor

moiety

identification

Triazine

breast-cancer

crystal-structure

Författare

Abdel Moneim El Massry

King Abdulaziz University

Alexandria University

A. M. Asal

Alexandria University

Serine N. Khattab

Alexandria University

N. S. Haiba

Alexandria University

H. A. Awney

Institute of Graduate Studies and Research

M. Helmy

Institute of Graduate Studies and Research

University of Hail

Vratislav Langer

Chalmers, Kemi- och bioteknik, Oorganisk miljökemi

Adel Amer

Alexandria University

Bioorganic and Medicinal Chemistry

0968-0896 (ISSN) 1464-3391 (eISSN)

Vol. 20 8 2624-2637

Ämneskategorier

Kemi

DOI

10.1016/j.bmc.2012.02.041