Synthesis and antiproliferative activity of two new tiazofurin analogues with 2′-amido functionalities

Popsavin, Mirjana; Torović, Ljilja; Svirčev, Miloš; Kojić, Vesna; Bogdanović, Gordana; Popsavin, Velimir

doi:10.1016/j.bmcl.2006.02.001

Cited by 52 publications

(23 citation statements)

References 15 publications

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“…C ‐aryl nucleosides, such as tiazofurin 1 , [2] are prototypical antiviral compounds as they can be recognized by cellular or viral polymerases, [3] while modifications to their structure lead to disruption and/or termination of replication [4] . C ‐aryl nucleosides, including 1 [5] and benzamide C ‐ribose 2 , [6] show antiproliferative activity (Scheme 1 A). Moreover, synthetic C ‐aryl nucleoside analogues, including 3 , are essential to studying the origins of mutagenicity and understanding the mechanism of replication and evolution [7] .…”

Section: Methodsmentioning

confidence: 99%

Diastereoselective Synthesis of Aryl C‐Glycosides from Glycosyl Esters via C−O Bond Homolysis

2021

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C‐aryl glycosyl compounds offer better in vivo stability relative to O‐ and N‐glycoside analogues. C‐aryl glycosides are extensively investigated as drug candidates and applied to chemical biology studies. Previously, C‐aryl glycosides were derived from lactones, glycals, glycosyl stannanes, and halides, via methods displaying various limitations with respect to the scope, functional‐group compatibility, and practicality. Challenges remain in the synthesis of C‐aryl nucleosides and 2‐deoxysugars from easily accessible carbohydrate precursors. Herein, we report a cross‐coupling method to prepare C‐aryl and heteroaryl glycosides, including nucleosides and 2‐deoxysugars, from glycosyl esters and bromoarenes. Activation of the carbohydrate substrates leverages dihydropyridine (DHP) as an activating group followed by decarboxylation to generate a glycosyl radical via C−O bond homolysis. This strategy represents a new means to activate alcohols as a cross‐coupling partner. The convenient preparation of glycosyl esters and their stability exemplifies the potential of this method in medicinal chemistry.

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Section: Methodsmentioning

confidence: 99%

Diastereoselective Synthesis of Aryl C‐Glycosides from Glycosyl Esters via C−O Bond Homolysis

2021

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“…For 16a the COMPARE analysis was run on a database of common anti-cancer agents (JobID: 37888) and the larger more comprehensive database including natural products and other submitted agents (JobID: 37889). The highest correlation coefficient achieved was 0.629 in relation to the synthetic nucleoside antitumour, DNA and RNA synthesis inhibitor tiazofurin [ 66 ]. CA-4 15 was listed as a high-ranking hit with a correlation coefficient of 0.658.…”

Section: Resultsmentioning

confidence: 99%

Novel Selective Estrogen Receptor Ligand Conjugates Incorporating Endoxifen-Combretastatin and Cyclofenil-Combretastatin Hybrid Scaffolds: Synthesis and Biochemical Evaluation

et al. 2017

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Nuclear receptors such as the estrogen receptors (ERα and ERβ) modulate the effects of the estrogen hormones and are important targets for design of innovative chemotherapeutic agents for diseases such as breast cancer and osteoporosis. Conjugate and bifunctional compounds which incorporate an ER ligand offer a useful method of delivering cytotoxic drugs to tissue sites such as breast cancers which express ERs. A series of novel conjugate molecules incorporating both the ER ligands endoxifen and cyclofenil-endoxifen hybrids covalently linked to the antimitotic and tubulin targeting agent combretastatin A-4 were synthesised and evaluated as ER ligands. A number of these compounds demonstrated pro-apoptotic effects, with potent antiproliferative activity in ER-positive MCF-7 breast cancer cell lines and low cytotoxicity. These conjugates displayed binding affinity towards ERα and ERβ isoforms at nanomolar concentrations e.g., the cyclofenil-amide compound 13e is a promising lead compound of a clinically relevant ER conjugate with IC50 in MCF-7 cells of 187 nM, and binding affinity to ERα (IC50 = 19 nM) and ERβ (IC50 = 229 nM) while the endoxifen conjugate 16b demonstrates antiproliferative activity in MCF-7 cells (IC50 = 5.7 nM) and binding affinity to ERα (IC50 = 15 nM) and ERβ (IC50 = 115 nM). The ER binding effects are rationalised in a molecular modelling study in which the disruption of the ER helix-12 in the presence of compounds 11e, 13e and 16b is presented These conjugate compounds have potential application for further development as antineoplastic agents in the treatment of ER positive breast cancers.

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“…They appear in the bacitracin, penicillin antibiotics [12], and various synthetic drugs as short-acting sulfa drug sulfathiazole [1]. Also, they are used as an antidepressant drug (pramipexole) [13], antiulcer agent (nizatidine) [14], anti-inflammatory drug (meloxicam) [15], HIV/AIDS drug (ritonavir) [16], and cancer treatment drug (tiazofurin) [17]. In fact, thiazole is a more common component of FDA-approved pharmaceuticals than related five-membered heterocycles such as isothiazole, thiophene, furan, isoxazole, and oxazole.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Thiazole Derivatives

Ibrahim¹,

Rizk²

2021

Azoles - Synthesis, Properties, Applications and Perspectives

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Thiazoles belong to the group of azole heterocycles. They are aromatic five-membered heterocycles containing one sulfur and one nitrogen atom. In recent years thiazoles, their derivatives, and isomers have gained considerable attention because of their broad applications in different fields, such as agrochemicals, industrial, and photographic sensitizers. Also, they have pharmaceutical and biological activities that include antimicrobial (sulfazole), antiretroviral (ritonavir), antifungal (abafungin), anticancer (tiazofurin), antidiabetic, anti-inflammatory, anti-Alzheimer, antihypertensive, antioxidant, and hepatoprotective activities. The compounds containing thiazole moieties are a prominent structural feature in a variety of natural products, such as vitamin B and penicillin. Thus, in this chapter several types of thiazole-based heterocyclic scaffolds such as monocyclic or bicyclic systems synthesis and their biological activities studies are presented. Furthermore modification of thiazole-based compounds at different positions to generate new molecules with potent antitumor, antioxidant, and antimicrobial activities is described.

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Synthesis and antiproliferative activity of two new tiazofurin analogues with 2′-amido functionalities

Cited by 52 publications

References 15 publications

Diastereoselective Synthesis of Aryl C‐Glycosides from Glycosyl Esters via C−O Bond Homolysis

Diastereoselective Synthesis of Aryl C‐Glycosides from Glycosyl Esters via C−O Bond Homolysis

Novel Selective Estrogen Receptor Ligand Conjugates Incorporating Endoxifen-Combretastatin and Cyclofenil-Combretastatin Hybrid Scaffolds: Synthesis and Biochemical Evaluation

Synthesis and Biological Evaluation of Thiazole Derivatives

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