New anionic poly(alkylideneamine) dendrimers as microbicide agents against HIV-1 infection

Maciel, Dina; Guerrero-Beltrán, Carlos Enrique; Ceña-Díez, Rafael; Tomás, Helena; Muñoz‐Fernández, María Ángeles; Rodrigues, João

doi:10.1039/c9nr00303g

Cited by 34 publications

(26 citation statements)

References 32 publications

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“…In the literature, there are several reports about the role of polyanions as entry inhibitors, especially against HIV infections (46,47). One of the main advantages of this interesting class over small-molecule drugs is their ability to bind to the target in a multivalent way, making them promising antiviral candidates (48). Comparison between our molecules and the established entry inhibitor DS (the control in this study) revealed numerous advantages, as AL439 and AL440 have a precise structure, welldefined composition, and moderate molecular size.…”

Section: Discussionmentioning

confidence: 99%

Tryptophan Trimers and Tetramers Inhibit Dengue and Zika Virus Replication by Interfering with Viral Attachment Processes

Fikatas

Vervaeke

Martínez-Gualda

et al. 2020

Antimicrob Agents Chemother

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Here, we report a class of tryptophan trimers and tetramers that inhibit (at low micromolar range) dengue and Zika virus infection in vitro. These compounds (AL family) have three or four peripheral tryptophan moieties directly linked to a central scaffold through their amino groups; thus, their carboxylic acid groups are free and exposed to the periphery. Structure-activity relationship (SAR) studies demonstrated that the presence of extra phenyl rings with substituents other than COOH at the N1 or C2 position of the indole side chain is a requisite for the antiviral activity against both viruses. The molecules showed potent antiviral activity, with low cytotoxicity, when evaluated on different cell lines. Moreover, they were active against laboratory and clinical strains of all four serotypes of dengue virus as well as a selected group of Zika virus strains. Additional mechanistic studies performed with the two most potent compounds (AL439 and AL440) demonstrated an interaction with the viral envelope glycoprotein (domain III) of dengue 2 virus, preventing virus attachment to the host cell membrane. Since no antiviral agent is approved at the moment against these two flaviviruses, further pharmacokinetic studies with these molecules are needed for their development as future therapeutic/prophylactic drugs.

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Section: Discussionmentioning

confidence: 99%

Tryptophan Trimers and Tetramers Inhibit Dengue and Zika Virus Replication by Interfering with Viral Attachment Processes

Fikatas

Vervaeke

Martínez-Gualda

et al. 2020

Antimicrob Agents Chemother

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“…Some of the dendrimers that may now be classified as “classic” include (i) poly(amidoamine) (PAMAM), which were developed by Tomalia in the 1980s, through an iterative reaction sequence between ethylenediamine and methyl ester moieties, and Michael addition with methyl acrylate on amines, in a divergent methodology [ 15 , 16 ]; and (ii) poly(ether), Fréchet dendrimers, prepared from 3,5-dihydroxy-benzyl bromide [ 17 ], in a convergent build-up on this core. Subsequently, several other interesting backbones of dendrimers/dendrons have been added [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], and include some earlier reports on silicon-containing dendrimers by Hadjichristidis [ 28 ]; polylysine by Denkewalter [ 29 ]; polyester by Newkome [ 30 ] and Ihre et al [ 31 ]; phosphorus-containing dendrimers by Caminade and Majoral [ 32 , 33 , 34 ]; polyether dendrimer via OsO 4 catalyzed oxidation of carbon-carbon double bonds [ 35 ]; peptide dendrimers [ 36 ]; amphiphilic PAMAM dendrimer with one dendritic block functionalized with sugar and the other with N -phthalic amide moieties [ 37 ]; and dendrimers for one-pot post bis-functionalization [ 38 ].…”

Section: Dendrimers/dendronsmentioning

confidence: 99%

Telodendrimers: Promising Architectural Polymers for Drug Delivery

Mejlsøe

Kakkar

2020

Molecules

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Architectural complexity has played a key role in enhancing the efficacy of nanocarriers for a variety of applications, including those in the biomedical field. With the continued evolution in designing macromolecules-based nanoparticles for drug delivery, the combination approach of using important features of linear polymers with dendrimers has offered an advantageous and viable platform. Such nanostructures, which are commonly referred to as telodendrimers, are hybrids of linear polymers covalently linked with different dendrimer generations and backbones. There is considerable variety in selection from widely studied linear polymers and dendrimers, which can help tune the overall composition of the resulting hybrid structures. This review highlights the advances in articulating syntheses of these macromolecules, and the contributions these are making in facilitating therapeutic administration. Limited progress has been made in the design and synthesis of these hybrid macromolecules, and it is through an understanding of their physicochemical properties and aqueous self-assembly that one can expect to fully exploit their potential in drug delivery.

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“…The therapeutic agents may either be encapsulated into the three-dimensional void spaces of the dendrimers or conjugated or physically adsorbed (electrostatic interactions) onto the surface of the dendrimer [ 11 , 12 ]. Another strategy is to develop dendrimers, such as drugs, active per se in several therapeutic realms [ [13] , [14] , [15] , [16] , [17] , [18] , [19] ]. Over the last several years, we have embarked on this direction in order to develop new drugs based on phosphorus dendrimers, for instance, as anticancer [ 20 , 21 ] and anti-inflammatory agents [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Non-invasive intranasal administration route directly to the brain using dendrimer nanoplatforms: An opportunity to develop new CNS drugs

Mignani

Shi

Karpus

et al. 2021

European Journal of Medicinal Chemistry

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There are several routes of administration to the brain, including intraparenchymal, intraventricular, and subarachnoid injections. The blood-brain barrier (BBB) impedes the permeation and access of most drugs to the central nervous system (CNS), and consequently, many neurological diseases remain undertreated. For past decades, to circumvent this effect, several nanocarriers have been developed to deliver drugs to the brain. Importantly, intranasal (IN) administration can allow direct delivery of drugs into the brain through the anatomical connection between the nasal cavity and brain without crossing the BBB. In this regard, dendrimers may possess great potential to deliver drugs to the brain by IN administration, bypassing the BBB and reducing systemic exposure and side effects, to treat diseases of the CNS. In this original concise review, we highlighted the few examples advocated regarding the use of dendrimers to deliver CNS drugs directly via IN. This review highlighed the few examples of the association of dendrimer encapsulating drugs ( e.g. , small compounds: haloperidol and paeonol; macromolecular compounds: dextran, insulin and calcitonin; and siRNA) using IN administration. Good efficiencies were observed. In addition, we will present the in vivo effects of PAMAM dendrimers after IN administration, globally, showing no general toxicity.

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New anionic poly(alkylideneamine) dendrimers as microbicide agents against HIV-1 infection

Abstract: This type of dendrimers, specifically the low-generation G1, can directly interact with the viruses, hampering their entry in the cells, preventing the HIV-1 infection without the need of combined therapy.

Cited by 34 publications

References 32 publications

Tryptophan Trimers and Tetramers Inhibit Dengue and Zika Virus Replication by Interfering with Viral Attachment Processes

Tryptophan Trimers and Tetramers Inhibit Dengue and Zika Virus Replication by Interfering with Viral Attachment Processes

Telodendrimers: Promising Architectural Polymers for Drug Delivery

Non-invasive intranasal administration route directly to the brain using dendrimer nanoplatforms: An opportunity to develop new CNS drugs

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