Current Developments in HIV Chemotherapy

Meadows, D. Christopher; Gervay‐Hague, Jacquelyn

doi:10.1002/cmdc.200500026

Cited by 58 publications

(44 citation statements)

References 100 publications

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“…Integrase is a viral protein of 32 kDa responsible for the insertion of newly reverse-transcribed doublestranded viral DNA into the host genome [48]. An IN inhibitor could offer improvements in selectivity, Ridley et al [50] reported that the sulfate group is critical for the anti-HIV-1 integrase activity of Lam-α 20-sulfate, because Lam-α showed no inhibition of HIV-1 integrase at concentrations up to 1.6 µM.…”

Section: Focus On Hiv Integrasementioning

confidence: 99%

Recent Advances in Lamellarin Alkaloids: Isolation, Synthesis and Activity

Plá¹,

Alberício²,

Álvarez

2008

ACAMC

106

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Lamellarins are a large family of marine alkaloids with potential anticancer activity that have been isolated from diverse marine organisms, mainly ascidians and sponges. All lamellarins feature a 3,4-diarylpyrrole system. Pentacyclic lamellarins, whose polyheterocyclic system has a pyrrole core, are the most active compounds. Some of these alkaloids are potently cytotoxic to various tumor cell lines. To date, Lam-D and Lam-H have been identified as lead compounds for the inhibition of topoisomerase I and HIV-1 integrase, respectively-nuclear enzymes which are over-expressed in deregulation disorders. Moreover, these compounds have been reported for their efficacy in treatment of multi-drug resistant (MDR) tumors cells without mediated drug efflux, as well as their immunomodulatory activity and selectivity towards melanoma cell lines. This article is an overview of recent literature on lamellarins, encompassing their isolation, recent synthetic strategies for their total synthesis, the preparation of their analogs, studies on their mechanisms of action, and their structure-activity relationships (SAR).

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Section: Focus On Hiv Integrasementioning

confidence: 99%

Recent Advances in Lamellarin Alkaloids: Isolation, Synthesis and Activity

Plá¹,

Alberício²,

Álvarez

2008

ACAMC

106

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“…Following the general procedure from 5-iodouracil 6 (1.55 g, 6.5 mmol) and after purification of the crude mixture by flash chromatography (CH 2 …”

Section: Methyl 5-deoxy-5-(24-dioxo-5-iodopyrimidin-1h-1-yl)-23-o-imentioning

confidence: 99%

“…The resulting mixture was purified by flash column chromatography on silica gel. The product was eluted with CH 2 . After evaporation of volatiles, the crude residue was purified by flash chromatography (CH 2 Cl 2 /MeOH 9:1).…”

Section: Methyl 5-deoxy-5-24-dioxo-5-[(2-trimethylsilyl)ethynyl]pyrmentioning

confidence: 99%

“…The mixture was filtered and the resin was washed with methanol. The combined filtrate was evaporated and the product was crystallized from CH 2 28,29 Reversed nucleoside derivatives 12−15 and 17, in a parallel with 5-fluorouracil 5 as a standard antitumor drug, were selected for preliminary in vitro testing on cytotoxicity using 6 different human tumor cell lines: cervix adenocarcinoma (HeLa), pancreatic carcinoma (MIAPaCa2), laryngeal carcinoma (Hep-2), human caucasian bronchioalveolar carcinoma (NCI-H358), and colon carcinoma (HT-29, CaCo2). The cells were grown in monolayer at 37 o C in a humidified atmosphere with 5 % CO 2 in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10 % (v/v) fetal bovine serum, 2 mM glutamine, 100 U penicillin and 100 mg/mL streptomycin.…”

Section: Methyl 5-deoxy-5-(24-dioxo-5-ethynylpyrimidin-1h-1-yl)-23-mentioning

confidence: 99%

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Synthesis and Biological Activity of Reversed Pyrimidine Nucleosides

et al. 2015

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Abstract. An efficient approach to reversed nucleosides which enables their synthesis in gram quantities is described. N-1′-Pyrimidine reversed nucleosides were prepared by treating of the sodium salt of pyrimidine bases with protected 5-tosyl ribose. Additionally, N-1′,N-3′-disubstituted reversed nucleosides were isolated in the condensation reactions with the 5-halogen pyrimidines. Using the Sonogashira coupling of 5′-iodouracil reversed nucleoside with ethynyltrimethyl silane gave 5′-ethynyl derivative which was further transformed into 5′-acetyl reversed nucleoside. Biological activity of deprotected reversed nucleosides was validated on the panel of six human carcinoma cell lines (HeLa, MIAPaCa2, Hep2, NCI-H358, CaCo-2, and HT-29). 5′-Iodouracil derivative displayed moderate growth inhibition activity against human colon carcinoma (CaCo-2) cells.

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“…However, the use of nucleoside antimetabolites also has the serious drawback that these agents may acquire drug resistance during clinical use. [10][11][12] To overcome this problem, the synthesis of diverse and structurally novel nucleoside derivatives is urgently needed in order to continue the search for new antitumor and antiviral agents.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4′-Thionucleosides as Antitumor and Antiviral Agents

Yoshimura

Saito

Natori

et al. 2018

CHEMICAL & PHARMACEUTICAL BULLETIN

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Many attempts have been made to synthesize structurally novel nucleoside derivatives in order to identify effective compounds for the treatment of tumors and virus-caused disease. At our laboratories, as part of our efforts to synthesize 4′-thionucleosides, we have identified and characterized biologically active nucleosides. During the course of our synthetic study, we developed the Pummerer-type thioglycosylation reaction. As a result, we synthesized a potent antineoplastic nucleoside, 1-(2-deoxy-2-fluoro-β-D-4-thio-arabinofuranosyl)cytosine (4′-thioFAC), and several novel 4′-thionucleosides that possess antiherpes virus activities.

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Current Developments in HIV Chemotherapy

Cited by 58 publications

References 100 publications

Recent Advances in Lamellarin Alkaloids: Isolation, Synthesis and Activity

Recent Advances in Lamellarin Alkaloids: Isolation, Synthesis and Activity

Synthesis and Biological Activity of Reversed Pyrimidine Nucleosides

Synthesis of 4′-Thionucleosides as Antitumor and Antiviral Agents

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