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Natural and synthetic acridines/acridones as antitumor agents: their biological activities and methods of synthesis

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Abstract

Acridine derivatives constitute a class of compounds that are being intensively studied as potential anticancer drugs. Acridines are well-known for their high cytotoxic activity; however, their clinical application is limited or even excluded because of side effects. Numerous synthetic methods are focused on the preparation of target acridine skeletons or modifications of naturally occurring compounds, such as acridone alkaloids, that exhibit promising anticancer activities. They have been examined in vitro and in vivo to test their importance for cancer treatment and to establish the mechanism of action at both the molecular and cellular level, which is necessary for the optimization of their properties so that they are suitable in chemotherapy. In this article, we review natural and synthetic acridine/acridone analogs, their application as anticancer drugs and methods for their preparation.

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Abbreviations

ABC:

ATP-binding cassette protein superfamily

ABCG2:

ATP-binding cassette, sub-family G (WHITE), member 2

CAN:

ceric ammonium nitrate

CDI:

1,1’-carbonyldiimidazole

DIPEA:

N,N-diisopropylethylamine

DMF:

N,N-dimethylformamide

DMP:

Dess-Martin reagent

EDCI:

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

HOBt:

1-hydroxybenzotriazole

IC50:

drug concentration at which 50% inhibition is observed

MDP:

N-acetyl-muramyl-L-alanyl-D-isoglutamine (muramyl dipeptide)

MS:

molecular sieves

NAD+:

nicotinamide adenine dinucleotide

NBS:

N-bromosuccinimide, NMO - N-methylmorpholine N-oxide

nor-MDP:

N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (nor-muramyl dipeptide)

ODNs:

oligodeoxynucleotides

PBO:

benzoyl peroxide, P-gp - P-glycoprotein

PTSA:

p-toluenesu-lfonic acid

TBS:

t-butyldimethylsilyl

TEBAC:

triethylben-zylammonium chloride

TMS:

trimethylsilyl

Topo:

topoisomerase

TPAP:

tetrapropyl ammoniumperruthenate

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  1. Department of Organic Chemistry, Gdansk University of Technology, Narutowicza 11/12, PL 80-233, Gdańsk, Poland

    Grzegorz Cholewiński, Krystyna Dzierzbicka & Aleksander M. Kołodziejczyk

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  1. Grzegorz Cholewiński
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  2. Krystyna Dzierzbicka
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  3. Aleksander M. Kołodziejczyk
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Correspondence to Grzegorz Cholewiński.

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Cholewiński, G., Dzierzbicka, K. & Kołodziejczyk, A.M. Natural and synthetic acridines/acridones as antitumor agents: their biological activities and methods of synthesis. Pharmacol. Rep 63, 305–336 (2011). https://doi.org/10.1016/S1734-1140(11)70499-6

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  • DOI: https://doi.org/10.1016/S1734-1140(11)70499-6

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