Synthesis and evaluation of new 2′,3′-dideoxynucleoside analogs as potential anti-AIDS and anti-herpes drugs

Faraj, Abdesslem; Maillard, Michel; Lemaître, M.; Letellier, S; Frappier, François; Florent, J.-C.; Grierson, D. S.; Monneret, Claude; Zerial, Aurelio

doi:10.1016/0223-5234(92)90102-7

Cited by 7 publications

(6 citation statements)

References 43 publications

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“…However, as the molecules studied by these authors correspond to only weakly active members of our series, this point required further evaluation. Thus, compounds 7, 12d, 12e, and 12q were incubated with recombinant HIV-1 RT 20 in the presence of poly(A)-oligo[dT (12)(13)(14)(15)(16)(17)(18) ] and poly(C)-oligo-[dG (12)(13)(14)(15)(16)(17)(18) ] template-primers, and the activities were monitored at varying concentrations (up to 100 µM). In contrast to AZT triphosphate, which was used as a control, none of these nucleosides displayed any significant inhibition of RT in the recombinant enzyme assays.…”

Section: Biological Results and Discussionmentioning

confidence: 99%

“…The AZT employed in this work was prepared by the reaction of the 5′-O-(thexyldimethylsilyl)-protected anhydrothymidine derivative 8 with NaN 3 in hot DMF, followed by O-deprotection of intermediate 9 (R ) thexyldimethylsilyl) (Scheme 1). 12 Although an excess of azide ion was generally used to obtain 9, on several occasions formation of minor amounts of the dimer 10 was also observed. The structure of this minor component was deduced from its NMR and mass spectra.…”

Section: Chemistrymentioning

confidence: 99%

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Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

et al. 1997

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A series of 22 derivatives of AZT substituted at the N-3 position of the thymine base were prepared and evaluated for anti-HIV activity in cell culture (Lai strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent displayed activities in the 0.045-0.082 microM range. The analogs 12d, 12e, 12q, 15, and 19 were active at <0.5 microM concentration. Compound 18 in which two molecules of AZT are connected at N-3 via a two-carbon link and "dimer" 11 also displayed significant activity. To obtain information concerning the mechanism of RT inhibition by these AZT analogs, compounds 7, 12d, 12e, and 12q were incubated with recombinant HIV-1 RT in the presence of poly(A)-oligo[dT(12-18)] and poly(C)-oligo[dG(12-18)] template-primers. In contrast to AZT-TP (control), none of these nucleosides displayed any significant inhibition of RT in the recombinant enzyme assay, indicating that phosphorylation is a necessary prerequisite for activity.

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Section: Biological Results and Discussionmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

et al. 1997

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“…Isocyanide analogues of thymine nucleoside were synthesized and evaluated as DNA chain terminator. Interestingly, the compound 290 proved to be cytotoxic with a cytotoxic dose (CD 50 ) of 8 and 20 μM against CEM and MRC-5 cells, while the formamide analogues were devoid of activity . The same compound and the uridine analogue 291 were tested as antiviral drugs against the HIV virus, but they proved to be inactive .…”

Section: Biological Activity Of Synthetic Isocyanidesmentioning

confidence: 96%

“…Interestingly, the compound 290 proved to be cytotoxic with a cytotoxic dose (CD 50 ) of 8 and 20 μM against CEM and MRC-5 cells, while the formamide analogues were devoid of activity. 272 The same compound and the uridine analogue 291 were tested as antiviral drugs against the HIV virus, but they proved to be inactive. 273 Compound 290 showed to be cytotoxic against MT-4 cell, with a CD 50 of 0.88 μM (Figure 66).…”

Section: Antiviralmentioning

confidence: 99%

Medicinal Chemistry of Isocyanides

et al. 2021

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In eons of evolution, isocyanides carved out a niche in the ecological systems probably thanks to their metal coordinating properties. In 1859 the first isocyanide was synthesized by humans and in 1950 the first natural isocyanide was discovered. Now, at the beginning of XXI century, hundreds of isocyanides have been isolated both in prokaryotes and eukaryotes and thousands have been synthesized in the laboratory. For some of them their ecological role is known, and their potent biological activity as antibacterial, antifungal, antimalarial, antifouling, and antitumoral compounds has been described. Notwithstanding, the isocyanides have not gained a good reputation among medicinal chemists who have erroneously considered them either too reactive or metabolically unstable, and this has restricted their main use to technical applications as ligands in coordination chemistry. The aim of this review is therefore to show the richness in biological activity of the isocyanidecontaining molecules, to support the idea of using the isocyanide functional group as an unconventional pharmacophore especially useful as a metal coordinating warhead. The unhidden hope is to convince the skeptical medicinal chemists of the isocyanide potential in many areas of drug discovery and considering them in the design of future drugs.

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“…It has been reported that chemically modified derivatives of F incorporating the 1,2,3‐triazole moiety showed antiviral activity whereas only a limited number of examples are known to exhibit anti‐cancer properties . Celewicz and co‐workers synthesized a series of novel 4‐chlorophenyl‐N‐alkyl phosphoramidites of 3’‐[4‐fluoroaryl‐(1,2,3‐triazole‐1‐yl)]‐3’‐deoxythymidine ( H ) and demonstrated anti‐cancer activity against the cervical (HeLa), nasopharyngeal (KB), breast (MCF‐7) and osteosarcoma (143B) human cancer cell lines over a wide range of concentrations .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anti‐Proliferative Activity of a Triazole‐Fused Thymidine Analogue

et al. 2020

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Here we report the synthesis of two-an acyclic and a macrocyclic-analogues of thymidine linked to a triazole moiety. The new molecules were synthesized through an intramolecular 1,3-dipolar cycloaddition reaction of the diazido derivative of thymidine with a suitable alkyne. The acyclic nucleoside showed dose dependent cytotoxicity against glioblastoma and breast cancer cells by causing significant cellular damage as studied with confocal laser scanning microscopy. In silico induced fit molecular docking studies showed poly(ADP-ribose) polymerase 1 (PARP1) as a potential target of the acyclic nucleoside. On the other hand, both the analogues showed no toxicity against normal fibroblast cells. ChemistrySelectCommunications

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Synthesis and evaluation of new 2′,3′-dideoxynucleoside analogs as potential anti-AIDS and anti-herpes drugs

Cited by 7 publications

References 43 publications

Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

Medicinal Chemistry of Isocyanides

Synthesis and Anti‐Proliferative Activity of a Triazole‐Fused Thymidine Analogue

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