301819-41-0Relevant articles and documents
Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors
Firoozpour, Loghman,Gao, Lixin,Moghimi, Setareh,Pasalar, Parvin,Davoodi, Jamshid,Wang, Ming-Wei,Rezaei, Zahra,Dadgar, Armin,Yahyavi, Hoda,Amanlou, Massoud,Foroumadi, Alireza
, p. 1674 - 1684 (2020/09/02)
ABTRACT: In this paper, a new series of isatin-sulphonamide based derivatives were designed, synthesised and evaluated as caspase inhibitors. The compounds containing 1-(pyrrolidinyl)sulphonyl and 2-(phenoxymethyl)pyrrolidin-1-yl)sulphonyl substitution at C5 position of isatin core exhibited better results compared to unsubstituted derivatives. According to the results of caspase inhibitory activity, compound 20d showed moderate inhibitory activity against caspase-3 and ?7 in?vitro compared to Ac-DEVD-CHO (IC50 = 0.016 ± 0.002 μM). Among the studied compounds, some active inhibitors with IC50s in the range of 2.33–116.91 μM were identified. The activity of compound 20d was rationalised by the molecular modelling studies exhibiting the additional van der Waals interaction of N-phenylacetamide substitution along with efficacious T-shaped π-π and pi-cation interactions. The introduction of compound 20d with good caspase inhibitory activity will help researchers to find more potent agents.
Structure-based design, synthesis, and biological evaluation of isatin derivatives as potential glycosyltransferase inhibitors
Wang, Yong,Chan, Fung-Yi,Sun, Ning,Lui, Hok-Kiu,So, Pui-Kin,Yan, Siu-Cheong,Chan, Kin-Fai,Chiou, Jiachi,Chen, Sheng,Abagyan, Ruben,Leung, Yun-Chung,Wong, Kwok-Yin
, p. 685 - 696 (2015/01/09)
Peptidoglycan glycosyltransferase (PGT) has been shown to be an important pharmacological target for the inhibition of bacterial cell wall biosynthesis. Structure-based virtual screening of about 3 000 000 commercially available compounds against the crystal structure of the glycosyltransferase (GT) domain of the Staphylococcus aureus penicillin-binding protein 2 (S. aureus PBP2) resulted in identification of an isatin derivative, 2-(3-(2-carbamimidoylhydrazono)-2-oxoindolin-1-yl)-N-(m-tolyl)acetamide (4) as a novel potential GT inhibitor. A series of 4 derivatives were synthesized. Several compounds showed more active antimicrobial activity than the initial hit compound 4, in particular 2-(3-(2-carbamimidoylhydrazono)-2-oxoindolin-1-yl)-N-(3-nitrophenyl)acetamide (4l), against Gram-positive Bacillus subtilis and S. aureus with MIC values of 24 and 48 lg/mL, respectively. Saturation transfer difference (STD) NMR study revealed that there is a binding contact between 4l and the GT domain of S. aureus PBP2. Competitive STD-NMR further proved that 4l and moenomycin A bind to GT domain in a competitive manner. Molecular docking study suggests a potential binding pocket of 4l in the GT domain of S. aureus PBP2. Taken together, compound 4l would provide a new scaffold for further development of potent GT inhibitors.
Design, synthesis, and QSAR study of novel 2-(2,3-dioxo-2,3- dihydro-1H-indol-1-yl)-N-phenylacetamide derivatives as cytotoxic agents
Modi, Neha R.,Shah, Ravi J.,Patel, Manish J.,Suthar, Maulik,Chauhan, Bhupendrasinh F.,Patel, Laxmanbhai J.
, p. 615 - 625 (2012/04/05)
This study deals with the synthesis of novel 2- (2,3-dioxo-2,3-dihydro-1H- indol-1-yl)-N-phenylacetamide derivatives (6a-j) from isatin (3) and 5,7-dibromoisatin (4). All newly synthesized compounds were characterized using IR, 1H NMR, MS, and elemental analysis followed by evaluation of their cytotoxic activity by XTT assay on breast cancer cell line MCF-7 and non-cancer African green monkey cell line VERO. Correlation study for QSAR and in vitro assay was performed. The outcomes indicated that electron withdrawing substitutions at para position of phenyl ring and 5, 7 positions of isatin ring and increasing lipophilicity of the compound increased the cytotoxic activity. The 2-(5,7-dibromo-2,3-dioxo-2,3-dihydro-1H-indol-1-yl)- N-(4-nitrophenyl)acetamide (6b) was found to be the most active compound in the series and demonstrated higher selectivity toward MCF-7 cell line. The IC50 values were 1.96 and 1.90 lM for test compound (6b) and vinblastin (reference drug), respectively. This indicates compound (6b) may possess equipotent cytotoxic activity to vinblastine. The compound (6b) is particularly promising, since it could kill cancer cells 19-20 times more effectively than the non-cancer cells. This property of (6b) may enable us to effectively control tumors with low side effects. Hence, we propose that 2-(5,7-dibromo-2,3-dioxo-2,3-dihydro-1Hindol- 1-yl)-N-(4-nitrophenyl)acetamide may be used as lead for further development. Springer Science+Business Media, LLC 2010.
