Modulation Effect on Tubulin Polymerization, Cytotoxicity and Antioxidant Activity of 1H-Benzimidazole-2-Yl Hydrazones.
Humans
Animals
Swine
Tubulin
/ metabolism
Antioxidants
/ pharmacology
Structure-Activity Relationship
Tubulin Modulators
/ pharmacology
Hydrazones
/ pharmacology
Molecular Docking Simulation
Polymerization
Drug Screening Assays, Antitumor
Antineoplastic Agents
/ pharmacology
Benzimidazoles
Molecular Structure
anticancer
antioxidant
benzimidazole
drug-likeness
molecular docking
tubulin polymerization
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
29 Dec 2022
29 Dec 2022
Historique:
received:
06
12
2022
revised:
22
12
2022
accepted:
25
12
2022
entrez:
8
1
2023
pubmed:
9
1
2023
medline:
11
1
2023
Statut:
epublish
Résumé
1H-benzimidazol-2-yl hydrazones with varying hydroxy and methoxy phenyl moieties were designed. Their effect on tubulin polymerization was evaluated in vitro on porcine tubulin. The compounds elongated the nucleation phase and slowed down the tubulin polymerization comparably to nocodazole. The possible binding modes of the hydrazones with tubulin were explored by molecular docking at the colchicine binding site. The anticancer activity was evaluated against human malignant cell lines MCF-7 and AR-230, as well as against normal fibroblast cells 3T3 and CCL-1. The compounds demonstrated a marked antineoplastic activity in low micromolar concentrations in both screened in vitro tumor models. The most active were the trimethoxy substituted derivative
Identifiants
pubmed: 36615483
pii: molecules28010291
doi: 10.3390/molecules28010291
pmc: PMC9822270
pii:
doi:
Substances chimiques
Tubulin
0
Antioxidants
0
Tubulin Modulators
0
Hydrazones
0
Antineoplastic Agents
0
Benzimidazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Bulgarian Science Fund
ID : КП-06-H39/4
Références
Eur J Med Chem. 2018 Feb 25;146:206-219
pubmed: 29407951
J Med Chem. 2013 May 9;56(9):3531-45
pubmed: 23600806
Int J Mol Sci. 2013 Jan 24;14(2):2410-30
pubmed: 23348932
iScience. 2020 Aug 29;23(9):101511
pubmed: 32920486
J Immunol Methods. 1983 Dec 16;65(1-2):55-63
pubmed: 6606682
Cold Spring Harb Perspect Biol. 2015 Jan 05;7(1):a020412
pubmed: 25561720
Curr Med Chem. 2009;16(1):21-41
pubmed: 19149561
J Agric Food Chem. 2004 Jan 14;52(1):48-54
pubmed: 14709012
Bioorg Chem. 2020 Jul;100:103929
pubmed: 32464404
J Med Chem. 2005 Apr 7;48(7):2270-3
pubmed: 15801819
Life Sci. 1998;63(19):1701-13
pubmed: 9806226
ACS Omega. 2022 Apr 28;7(18):16152-16163
pubmed: 35571854
Phys Chem Chem Phys. 2011 Apr 21;13(15):7178-88
pubmed: 21409256
Cancer Biother Radiopharm. 2010 Apr;25(2):245-50
pubmed: 20423239
Chem Biodivers. 2008 Nov;5(11):2171-336
pubmed: 19035562
Biochimie. 1999 Jan-Feb;81(1-2):59-67
pubmed: 10214911
J Med Chem. 2002 Jun 6;45(12):2615-23
pubmed: 12036371
Biol Signals Recept. 1998 Jul-Aug;7(4):195-219
pubmed: 9730580
Nat Rev Drug Discov. 2015 Jun;14(6):387-404
pubmed: 25907346
Neuro Endocrinol Lett. 2010;31 Suppl 1:1-42
pubmed: 20881933
Adv Drug Deliv Rev. 2009 Apr 28;61(4):290-302
pubmed: 19249331
Int J Mol Sci. 2019 May 10;20(9):
pubmed: 31083440
Int J Cancer. 2001 Oct 1;94(1):89-96
pubmed: 11668483
In Vivo. 2011 Jan-Feb;25(1):49-53
pubmed: 21282734
FEBS J. 2016 Jan;283(1):102-11
pubmed: 26462166
Curr Opin Drug Discov Devel. 2009 Mar;12(2):240-5
pubmed: 19333869
Curr Top Med Chem. 2018;18(12):987-997
pubmed: 30051792
Oncology. 1991;48(6):448-50
pubmed: 1749579
ISRN Pharm. 2012;2012:195727
pubmed: 22830056
J Agric Food Chem. 2001 Oct;49(10):4619-26
pubmed: 11599998
Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
pubmed: 11259830
Comp Biochem Physiol A Mol Integr Physiol. 1998 Feb;119(2):493-501
pubmed: 11248993
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1358-62
pubmed: 24997336
Arch Pharm (Weinheim). 1999 Apr;332(4):115-23
pubmed: 10327884
Eur J Med Chem. 2022 Nov 5;241:114614
pubmed: 35939994
RSC Adv. 2021 Dec 14;11(63):39848-39868
pubmed: 35494105
J Agric Food Chem. 2002 May 8;50(10):2772-7
pubmed: 11982397
Drug Metab Rev. 2002 Feb-May;34(1-2):17-35
pubmed: 11996009
ChemMedChem. 2016 Jun 6;11(11):1117-21
pubmed: 27218427
Eur J Cancer Clin Oncol. 1987 Jul;23(7):949-57
pubmed: 3666000
Neuro Endocrinol Lett. 2002 Apr;23 Suppl 1:39-44
pubmed: 12019350
Nature. 2005 May 26;435(7041):519-22
pubmed: 15917812
Farmaco. 2004 Feb;59(2):83-91
pubmed: 14871499
Bioorg Med Chem. 2010 Jul 15;18(14):4905-16
pubmed: 20598555
Cancer Lett. 2009 Sep 18;282(2):125-36
pubmed: 19185987
Molecules. 2016 Apr 30;21(5):
pubmed: 27144551
Chem Biol Interact. 2021 Aug 25;345:109540
pubmed: 34139148
Int J Radiat Oncol Biol Phys. 2004 Jul 1;59(3):639-53
pubmed: 15183467
Eur J Pharm Sci. 2010 Nov 20;41(3-4):452-7
pubmed: 20656026
Eur J Med Chem. 2011 Jun;46(6):2274-9
pubmed: 21439689