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The trimethoxyphenyl (TMP) functional group: a versatile pharmacophore

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Abstract

The Trimethoxyphenyl (TMP) group serves as a pharmacophore in numerous potent agents exhibiting diverse bioactivity effects. This moiety is prominently present in the molecular structures of various research studies, demonstrating remarkable multi-activity or specific targeting, surpassing the activity of other derivatives at comparable concentrations. The compounds containing the TMP group have displayed notable anti-cancer effects by effectively inhibiting tubulin, heat shock protein 90 (Hsp90), thioredoxin reductase (TrxR), histone lysine-specific demethylase 1 (HLSD1), activin receptor-like kinase-2 (ALK2), P-glycoprotein (P-gp), and platelet-derived growth factor receptor β. Furthermore, select TMP-bearing compounds have shown promising anti-fungal and anti-bacterial properties, including activities against Helicobacter pylori and Mycobacterium tuberculosis. Additionally, there have been reports on the antiviral activity of TMP-based compounds, which hold potential against viruses such as the acquired immunodeficiency syndrome (AIDS) virus, hepatitis C virus, and influenza virus. Compounds containing the TMP pharmacophore have also demonstrated significant efficacy against Leishmania, Malaria, and Trypanosoma, indicating their potential as anti-parasitic agents. Furthermore, these compounds have been associated with anti-inflammatory, anti-Alzheimer, anti-depressant, and anti-migraine properties, thereby expanding their therapeutic scope. This paper presents a comprehensive and categorized review of these diverse properties of TMP-bearing compounds, shedding light on their potential as valuable agents across a wide range of biomedical applications.

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Abbreviations

TMP :

trimethoxyphenyl;

DHFR :

dihydrofolate reductase

CA :

combretastatin

CBS :

colchicine binding site

Hsp90 :

heat shock protein90

TrxR :

thioredoxin reductase

HLSD1 :

histone lysine-specific demethylase 1

ALK2 :

activin receptor-like kinase-2

VEGFR2 :

vascular endothelial growth factor 2

P-gp :

P-glycoprotein

PAF :

platelet-activating factor

COX-1 and COX-2 :

cyclooxygenase 1 and 2

ALS :

amyotrophic lateral sclerosis

EGFR :

endothelial growth factor receptor

WHO :

world health organization

MTT :

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide

DPPH :

2,2-diphenyl-1-picrylhydrazyl free radical

NDI :

1,4,5,8-naphthalenetetracarboxylic diimide

ERK2 :

Extracellular Signal Regulated Kinase 2

MTAs :

Microtubules targeting agents

MAPs :

microtubule-associated proteins

ITP :

inhibitions of tubulin polymerization

GTP :

guanosine triphosphate

TPI :

tubulin polymerization inhibitory

IC 50 :

half-maximal inhibitory concentration

CC 50 :

median cytotoxic concentration, compound concentration (μM) required to reduce the viability of mock-infected MT-4 cells by 50%, as determined by the MTT method

GI 50 :

growth inhibitory 50%

EC 50 :

half maximal effective concentration

LD 50 :

lethal dose 50%

PDGF-Rβ :

platelet-derived growth factor receptor β

MIC :

minimal inhibitory concentration

HCV :

hepatitis C virus

GAK :

Cyclin-G associated kinase

SAR :

structure-activity relationship

FP-2 :

falcipain-2

NF-Κb :

Nuclear factor kappa B

MAPKs :

mitogen-activated protein kinases

TNF-α :

tumor necrosis factor alpha

IL-6 :

interleukin 6

TGI :

total growth inhibition

ALI :

acute lung injury

NO :

nitric oxide

LPS :

lipopolysaccharides

TLR4 :

toll-like receptor 4

AChE :

acetylcholinesterase enzyme

FKBP51 :

FK506-binding protein 51

5-HT2B :

5-hydroxytryptamine receptor 2B

ED 50 :

median effective dose

MAPs :

microtubule-associated proteins

PL :

piperlongumine

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Acknowledgements

This research project received financial backing from Kerman University of Medical Sciences under the project number 98000181, with ethical approval granted under code IR.KMU.REC.1398.158.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

    Mohammad Amin Langarizadeh, Alieh Ameri & Marziye Ranjbar Tavakoli

  2. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Alieh Ameri

  3. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA

    Ardavan Abiri

  4. Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, CT, 06520, USA

    Ardavan Abiri

  5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

    Hamid Forootanfar

  6. Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran

    Hamid Forootanfar

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Langarizadeh, M.A., Ameri, A., Tavakoli, M.R. et al. The trimethoxyphenyl (TMP) functional group: a versatile pharmacophore. Med Chem Res 32, 2473–2500 (2023). https://doi.org/10.1007/s00044-023-03153-4

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