Aziridine alkaloids as potential therapeutic agents

Ismail, Fyaz M.D.; Levitsky, Dmitrii I.; Dembitsky, Valery M.

doi:10.1016/j.ejmech.2009.05.013

Cited by 216 publications

(99 citation statements)

References 106 publications

(155 reference statements)

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“…The cytotoxic mechanism of this alkaloid includes the alkylation of DNA, the generation of oxygen radicals and the inhibition of DNA and RNA synthesis. Other aziridine alkaloids isolated from nature have also displayed anticancer activity (3). These data suggest that compounds containing aziridine in their structure could have potential anticancer activity.…”

Section: Introductionmentioning

confidence: 83%

“…The aziridine group is present in the structure of useful reaction intermediates in organic chemistry and also in a variety of secondary metabolites from plants and microorganisms (3,4). Many of these compounds have displayed anticancer activity (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Although the main mechanism of this drug remains unclear, it is thought that the aziridyl groups of thiotepa induce cross-links with DNA, interfering with DNA replication and cell division (9). Mitomycin C is an aziridine alkaloid isolated from Streptomyces bacteria (3,10). This anticancer drug is useful for the treatment of gastric and pancreatic adenocarcinomas.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Anticancer Activity and Mechanism of Action of an Aziridinyl Galactopyranoside

Burgos-Morón¹,

N²,

Ml³

et al. 2018

Preprint

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We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[N-(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-β-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore possible mechanisms involved in the cytotoxicity of this aziridine and evaluate its selective anticancer activity using cancer cells and normal cells from a variety of tissues. Our data show that AzGalp induces DNA damage (detected with the comet assay). Cells deficient in the DNA repair pathway nucleotide excision repair (NER) were hypersensitive to the cytotoxicity of this compound. These results suggest that AzGalp induces bulky DNA adducts, and that cancer cells lacking a functional NER pathway may be particularly vulnerable to the anticancer effects of this aziridine. Several experiments revealed that neither the generation of oxidative stress nor the inhibition of glycolysis played a significant role in the cytotoxicity of AzGalp. The combinations of AzGalp with either oxaliplatin or 5-fluorouracil slightly improved the ability of both anticancer drugs to selectively kill cancer cells. AzGalp also displayed selective cytotoxicity against a panel of malignant cells versus normal cells; the highest selectivity was observed for two acute promyelocytic leukemia cell lines. Additional preclinical studies are necessary to evaluate the anticancer potential of AzGalp.

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Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vitro Anticancer Activity and Mechanism of Action of an Aziridinyl Galactopyranoside

Burgos-Morón¹,

N²,

Ml³

et al. 2018

Preprint

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“…Interest in this small heterocycle is dictated either by biological activity, mainly as antitumor agents, displayed by some naturally occurring compounds bearing the aziridine ring or by the ring strain of those spring-loaded heterocycles that make them useful precursors of more complex molecules. [6][7][8] The highly strained three-membered ring readily opens with excellent stereo-and regioselectivity to afford a wide variety of more stable ring-opened or ring-expanded amines. Chiral aziridines have found widespread use in organic synthesis.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of chiral 1-(2-aminoalkyl)aziridines via the self-opening reaction of aziridine

Pieczonka¹,

Misztal²,

Rachwalski³

et al. 2016

Arkivoc

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“…In addition, heterocyclic compounds carrying isoxazolines units have also a pharmaceutical importance and some of them posse's anticancer 22 , antimicrobial 23 , anticoagulant 2 , and anti inflammatory 24 activity. It was revealed that aziridine ring is an element of a large number of natural products type alkaloids 25 and various biologically active compounds such as antibiotics 26 and antitumor agents 27 . Because of their broad spectrum of biological activities and pharmacological properties 28 , many efficient and more general synthetic strategies have been developed for the preparation of aziridines 29 .…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of antimicrobial, anticoagulant, and anticholinesterase hybrid molecules from 4-methylumbelliferone

Zayane

Rahmouni

Daami‐Remadi

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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We designed and synthesized new series of diverse triazoles, isoxazoles, isoxazolines, and aziridines linked 4-methylumbelliferone 1 using intermolecular 1,3-dipolar cycloaddition reactions. Structures of these compounds were established on the basis of 1 H NMR, 13 C NMR, and ESI-HRMS. All prepared compounds were evaluated for their antimicrobial, anticoagulant, and anticholinesterase activities. Interestingly, among the tested molecules, some of the analogs displayed better activities than the parent 4-methylumbelliferone 1 such as 6a and 6d for their antifungal properties. Moreover, compounds 4, 5, 6, and 7 showed the importance of the added fragments to 4-methylumbelliferone 1 via the linker methylene to have good activity.

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Aziridine alkaloids as potential therapeutic agents

Cited by 216 publications

References 106 publications

<em></em><em>In Vitro</em> Anticancer Activity and Mechanism of Action of an Aziridinyl Galactopyranoside

<em></em><em>In Vitro</em> Anticancer Activity and Mechanism of Action of an Aziridinyl Galactopyranoside

Synthesis of chiral 1-(2-aminoalkyl)aziridines via the self-opening reaction of aziridine

Design and synthesis of antimicrobial, anticoagulant, and anticholinesterase hybrid molecules from 4-methylumbelliferone

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