NDLI: Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study

Content Provider	Royal Society of Chemistry (RSC)
Author	Yan, Xingchen Wu, Xiaojing Zhang, Zhongyu Bi, Caifeng Zhang, Xia Xu, Jiakun Fan, Yuhua
Copyright Year	2015
Abstract	Nine compounds were designed and synthesized by the condensation reaction of the carbonyl in 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (HPMBP) with the amino groups in 5-aminoisophthalic acid, 4,4′-diaminodiphenylmethane, 4-aminophenylacetic acid, 4-aminobenzamide, 2-amino-4-methylphenol, 5-amino-2-methylphenol, 2-aminophenol, 3-aminophenol and 4-aminophenol. They were then characterized by IR, 1H NMR, elemental analysis, and X-ray crystallography, which suggested that all of them exist as the pyrazolone-enamine forms in the solid state and in a DMSO solution through tautomeric reactions. The nine compounds (compounds 1–9) were evaluated for their ability to inhibit the proliferation of human liver cancer HepG2 cells. Compounds 5, 6, 7 and 8 demonstrated a strong inhibitory effect on the proliferation of HepG2 cells. The nine compounds can also inhibit the activity of the human cancer cellular 20S proteasome. Further studies on compound 6 as the representative indicate that it can cause the accumulation of ubiquitinated proteins and the proteasome target proteins Bax and p27, and exhibit a cytostatic effect in HepG2 cells in a concentration-dependent and time-dependent manner. The four potential tautomers of compound 6 were optimized and their single point energies were calculated by the density functional theory (DFT) B3LYP method based on the polarized continuum model (PCM) in water to identify the most likely tautomer existing in cancer cells. Based on the optimized structure of the most stable tautomer in water, the Wiberg bond orders, molecular electrostatic potential (MEP) maps and frontier molecular orbital were calculated. As compounds 5, 6, 7 and 8 have hydroxyl in the ortho-position or meta-position, our study can provide some information to study their anticancer mechanism and the substitution effect of different functional groups.
Starting Page	2168
Ending Page	2180
Page Count	13
File Format	HTM / HTML PDF
ISSN	11440546
Volume Number	39
Issue Number	3
Journal	New Journal of Chemistry
DOI	10.1039/c4nj01906g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Molecular orbital Wiberg DMSO Benzoyl group Hepatocellular carcinoma X-ray crystallography Hydroxy group Carboxylic acid P-Cresol Aminophenol Density functional theory Carbonyl group Nuclear magnetic resonance Proteasome Condensation reaction Phenyl group Tautomer Bcl-2-associated X protein Dimethyl sulfoxide Bax Covalent bond Non-mevalonate pathway Phase-contrast microscopy Electrostatics Cancer
Content Type	Text
Resource Type	Article
Subject	Chemistry Materials Chemistry Catalysis

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

BAX/BCL-2 mRNA and protein expression in human breast MCF-7 cells exposed to drug vehicles-methanol and dimethyl sulfoxide (DMSO) for 24 hrs.

A practical improvement of odorless Corey–Kim and Swern oxidations

BAX/BCL-2 mRNA and protein expression in human breast MCF-7 cells exposed to drug vehicles-methanol and dimethyl sulfoxide (DMSO) for 24 hrs

The effect of DMSO in the aqueous thiol–disulphide dynamic covalent chemistry of model pseudopeptides

Ferrocene based organometallic gelators: a supramolecular synthon approach

Organophosphorus intermediates. Part III. The base-catalysed addition of methyl phenylphosphinate, dimethyl phosphonate, and diphenylphosphine oxide to tetraphenylcyclopentadienone

Positive and negative allosteric effects of thiacalix[4]arene-based receptors having urea and crown-ether moieties

Metal-free synthesis of 3-methylthiofurans from homopropargylic alcohols and DMSO via a tandem sulfenylation/cyclization reaction in a one-pot manner

Strategies in developing dimethyl sulfoxide (DMSO)-free cryopreservation protocols for biotherapeutics

Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study

Similar Documents

BAX/BCL-2 mRNA and protein expression in human breast MCF-7 cells exposed to drug vehicles-methanol and dimethyl sulfoxide (DMSO) for 24 hrs.

A practical improvement of odorless Corey–Kim and Swern oxidations

BAX/BCL-2 mRNA and protein expression in human breast MCF-7 cells exposed to drug vehicles-methanol and dimethyl sulfoxide (DMSO) for 24 hrs

The effect of DMSO in the aqueous thiol–disulphide dynamic covalent chemistry of model pseudopeptides

Ferrocene based organometallic gelators: a supramolecular synthon approach

Organophosphorus intermediates. Part III. The base-catalysed addition of methyl phenylphosphinate, dimethyl phosphonate, and diphenylphosphine oxide to tetraphenylcyclopentadienone

Positive and negative allosteric effects of thiacalix[4]arene-based receptors having urea and crown-ether moieties

Metal-free synthesis of 3-methylthiofurans from homopropargylic alcohols and DMSO via a tandem sulfenylation/cyclization reaction in a one-pot manner

Strategies in developing dimethyl sulfoxide (DMSO)-free cryopreservation protocols for biotherapeutics

Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study