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Synthesis, crystal structures, antiproliferative activities and reverse docking studies of eight novel Schiff bases derived from benzil
Author(s) -
Tan Xue-Jie,
Wang Di,
Hei Xiao-Ming,
Yang Feng-Cun,
Zhu Ya-Ling,
Xing Dian-Xiang,
Ma Jian-Ping
Publication year - 2020
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229619015687
Subject(s) - benzil , chemistry , schiff base , cytotoxicity , stereochemistry , in vitro , mtt assay , proton nmr , organic chemistry , biochemistry , catalysis
Eight novel Schiff bases derived from benzil dihydrazone ( BDH ) or benzil monohydrazone ( BMH ) and four fused‐ring carbonyl compounds (3‐formylindole, FI ; 3‐acetylindole, AI ; 3‐formyl‐1‐methylindole, MFI ; 1‐formylnaphthalene, FN ) were synthesized and characterized by elemental analysis, ESI–QTOF–MS, 1 H and 13 C NMR spectroscopy, as well as single‐crystal X‐ray diffraction. They are (1 Z ,2 Z )‐1,2‐bis{( E )‐[(1 H ‐indol‐3‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethane ( BDHFI ), C 32 H 24 N 6 , (1 Z ,2 Z )‐1,2‐bis{( E )‐[1‐(1 H ‐indol‐3‐yl)ethylidene]hydrazinylidene}‐1,2‐diphenylethane ( BDHAI ), C 34 H 28 N 6 , (1 Z ,2 Z )‐1,2‐bis{( E )‐[(1‐methyl‐1 H ‐indol‐3‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethane ( BMHMFI ) acetonitrile hemisolvate, C 34 H 28 N 6 ·0.5CH 3 CN, (1 Z ,2 Z )‐1,2‐bis{( E )‐[(naphthalen‐1‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethane ( BDHFN ), C 36 H 26 N 4 , ( Z )‐2‐{( E )‐[(1 H ‐indol‐3‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethanone ( BMHFI ), C 23 H 17 N 3 O, ( Z )‐2‐{( E )‐[1‐(1 H ‐indol‐3‐yl)ethylidene]hydrazinylidene}‐1,2‐diphenylethanone ( BMHAI ), C 24 H 19 N 3 O, ( Z )‐2‐{( E )‐[(1‐methyl‐1 H ‐indol‐3‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethanone ( BMHMFI ), C 24 H 19 N 3 O, and ( Z )‐2‐{( E )‐[(naphthalen‐1‐yl)methylidene]hydrazinylidene}‐1,2‐diphenylethanone ( BMHFN ) C 25 H 18 N 2 O. Moreover, the in vitro cytotoxicity of the eight title compounds was evaluated against two tumour cell lines (A549 human lung cancer and 4T 1 mouse breast cancer) and two normal cell lines (MRC‐5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that four ( BDHMFI , BDHFN , BMHMFI and BMHFN ) are inactive and the other four ( BDHFI , BDHAI , BMHFI and BMHAI ) show severe toxicities against human A549 and mouse 4T 1 cells, similar to the standard cisplatin. All the compounds exhibited weaker cytotoxicity against normal cells than cancer cells. The Swiss Target Prediction web server was applied for the prediction of protein targets. After analyzing the differences in frequency hits between these active and inactive Schiff bases, 18 probable targets were selected for reverse docking with the Surflex‐dock function in SYBYL‐X 2.0 software. Three target proteins, i.e. human ether‐á‐go‐go‐related (hERG) potassium channel, the inhibitor of apoptosis protein 3 and serine/threonine‐protein kinase PIM1, were chosen as the targets. Finally, the ligand‐based structure–activity relationships were analyzed based on the putative protein target (hERG) docking results, which will be used to design and synthesize novel hERG ion channel inhibitors.