Synthesis and Biological Evaluation of Amidinourea Derivatives against Herpes Simplex Viruses

Toscani, Anita; Rossana, Denaro; Pacheco, Sergio Fernando Castillo; Biolatti, Matteo; Anselmi, S; Dell’Oste, Valentina; Castagnolo, Daniele

doi:10.3390/molecules26164927

Cited by 8 publications

(14 citation statements)

References 27 publications

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“…It was also shown that the tested substances have a different mechanism of action than the nucleotide analogues. They act on the early stages of virus replication [ 151 ]. MBZM-N-IBT1-[(2-methyl benzimidazole-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea is also in preclinical testing.…”

Section: Compounds With Potential Use In the Treatment Of Herpesvirus...mentioning

confidence: 99%

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

Majewska

Młynarczyk-Bonikowska

2022

IJMS

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Herpes simplex virus types 1 and 2 HSV1 and 2, namely varicella-zoster VZV and cytomegalovirus CMV, are among the most common pathogens worldwide. They remain in the host body for life. The course of infection with these viruses is often asymptomatic or mild and self-limiting, but in immunocompromised patients, such as solid organ or bone marrow transplant recipients, the course can be very severe or even life-threatening. Unfortunately, in the latter group, the highest percentage of infections with strains resistant to routinely used drugs is observed. On the other hand, frequent recurrences of genital herpes can be a problem even in people with normal immunity. Genital herpes also increases the risk of acquiring sexually transmitted diseases, including HIV infection and, if present in pregnant women, poses a risk to the fetus and newborn. Even more frequently than herpes simplex, congenital infections can be caused by cytomegalovirus. We present the most important anti-herpesviral agents, the mechanisms of resistance to these drugs, and the associated mutations in the viral genome. Special emphasis was placed on newly introduced drugs such as maribavir and brincidofovir. We also briefly discuss the most promising substances in preclinical testing as well as immunotherapy options and vaccines currently in use and under investigation.

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Section: Compounds With Potential Use In the Treatment Of Herpesvirus...mentioning

confidence: 99%

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

Majewska

Młynarczyk-Bonikowska

2022

IJMS

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“…Within this time frame, there were two (1.46%) studies in 2015 [ 6 , 7 ], 15 (10.95%) studies in 2016 [ 1 , 3 , 8 - 20 ], 19 (13.87%) studies in 2017 [ 21 - 39 ], 27 (19.71%) studies in 2018 [ 40 - 64 ], 23 (16.79%) studies in 2019 [ 2 , 65 - 86 ], 24 (17.52%) studies in 2020 [ 87 - 110 ], and 27 (19.70%) studies in 2021 [ 111 - 137 ]. Regarding the type of studies reviewed, 121 (88.32%) studies included in vitro elements [ 2 , 3 , 6 - 12 , 14 - 20 , 23 - 26 , 28 - 42 , 44 - 47 , 49 - 56 , 58 - 64 , 66 , 68 - 72 , 74 - 77 , 79 , 80 , 82 - 87 , 89 - 118 , 120 , 122 - 133 , 135 - 139 ] and 23 (16.79%) in vivo [ 2 , 13 , 15 , 18 , 22 , 25 , 27 , 28 , 37 , 43 , 48 , 56 , 62 , 67 , 73 , 78 , 81 , 100 , …”

Section: Reviewmentioning

confidence: 99%

“…Sample size was extremely variable and unable to be compared due to the differences in study designs. In terms of sample characteristics, 99 (72.26%) studies used Vero cells [ 2 , 3 , 6 , 8 - 10 , 14 - 20 , 23 , 25 , 26 , 28 , 30 - 34 , 36 , 39 - 42 , 44 - 47 , 50 , 51 , 53 - 56 , 58 - 64 , 66 - 70 , 72 , 74 , 76 , 77 , 79 , 82 , 83 , 85 - 87 , 89 - 95 , 97 - 108 , 111 - 113 , 115 - 118 , 120 , 122 , 123 , 125 - 130 , 132 , 133 , 135 , 137 , 138 ], 41 (29.93%) used human cell lines [ 7 , 11 , 12 , 16 , 19 , 24 , 29 , 31 , 36 , 38 , 47 , 49 , 52 - 56 , 61 , 62 , 67 ,…”

Section: Reviewmentioning

confidence: 99%

“…Regarding which viruses the interventions were tested on, 113 (82.48%) studies used HSV-1 [ 1 - 3 , 6 - 16 , 19 , 21 - 27 , 29 - 31 , 33 - 35 , 37 , 38 , 40 - 44 , 46 - 49 , 51 , 53 - 56 , 60 - 65 , 67 - 74 , 76 - 79 , 82 , 83 , 85 - 99 , 103 - 123 , 125 - 134 , 136 - 138 ], 61 (44.53%) studies used HSV-2 [ 7 - 11 , 14 - 20 , 25 , 27 , 28 , 30 - 33 , 35 - 37 , 39 , 44 - 53 , 55 , 58 , 59 , 61 , 66 , 69 , 73 , 75 , 81 , 83 , 85 , 89 , 91 , 93 , 100 , 102 , 104 , 105 , 108 - 110 , 118 , ...…”

Section: Reviewmentioning

confidence: 99%

“…We have shown that a majority of the studies reviewed have efficacy as potential managements for resistant strains of HSV [ 1 - 3 , 6 - 20 , 22 - 45 , 47 - 52 , 54 - 56 , 58 - 83 , 85 - 106 , 108 - 125 , 127 - 130 , 132 - 138 ]. The predominance of studies utilized Vero cells [ 2 , 3 , 6 , 8 - 10 , 14 - 20 , 23 , 25 , 26 , 28 , 30 - 34 , 36 , 39 - 42 , 44 - 47 , 50 , 51 , 53 - 56 , 58 - 64 , 66 - 70 , 72 , 74 , 76 , 77 , 79 , 82 , 83 , 85 - 87 , 89 - 95 , 97 - 108 , 111 - 113 , 115 - 118 , 120 , 122 , 123 , 125 - 130 , 132 , 133 , 135...…”

Section: Reviewmentioning

confidence: 99%

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A Systematic Review of Second-Line Treatments in Antiviral Resistant Strains of HSV-1, HSV-2, and VZV

Lince¹,

DeMario²,

Yang³

et al. 2023

Cureus

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Drug-resistant variants of herpes simplex viruses (HSV) have been reported that are not effectively treated with first-line antiviral agents. The objective of this study was to evaluate available literature on the possible efficacy of second-line treatments in HSV and the use of second-line treatments in HSV strains that are resistant to first-line treatments. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a final search was conducted in six databases on November 5, 2021 for all relevant literature using terms related to antiviral resistance, herpes, and HSV. Eligible manuscripts were required to report the presence of an existing or proposed second-line treatment for HSV-1, HSV-2, or varicella zoster virus (VZV); have full-text English-language access; and potentially reduce the rate of antiviral resistance. Following screening, 137 articles were included in qualitative synthesis. Of the included studies, articles that examined the relationship between viral resistance to first-line treatments and potential second-line treatments in HSV were included. The Cochrane risk-of-bias tool for randomized trials was used to assess risk of bias. Due to the heterogeneity of study designs, a meta-analysis of the studies was not performed. The dates in which accepted studies were published spanned from 2015-2021. In terms of sample characteristics, the majority (72.26%) of studies used Vero cells. When looking at the viruses on which the interventions were tested, the majority (84.67%) used HSV-1, with (34.31%) of these studies reporting testing on resistant HSV strains. Regarding the effectiveness of the proposed interventions, 91.97% were effective as potential managements for resistant strains of HSV. Of the papers reviewed, nectin in 2.19% of the reviews had efficacy as a second-line treatments in HSV, amenamevir in 2.19%, methanol extract in 2.19%, monoclonal antibodies in 1.46%, arbidol in 1.46%, siRNA swarms in 1.46%, Cucumis melo sulfated pectin in 1.46%, and components from Olea europeae in 1.46%. In addition to this griffithsin in 1.46% was effective, Morus alba L. in 1.46%, using nucleosides in 1.46%, botryosphaeran in 1.46%, monoterpenes in 1.46%, almond skin extracts in 1.46%, bortezomib in 1.46%, flavonoid compounds in 1.46%, andessential oils were effective in 1.46%, but not effective in 0.73%. The available literature reviewed consistently supports the existence and potentiality of second-line treatments for HSV strains that are resistant to first-line treatments. Immunocompromised patients have been noted to be the population most often affected by drug-resistant variants of HSV. Subsequently, we found that HSV infections in this patient population are challenging to manage clinically effectively. The goal of this systematic review is to provide additional information to patients on the potentiality of second-line treatment in HSV strains resistant to first-line treatments, especially those who are immunocompromised. All patients,...

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Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5‐Triazin‐2‐one Ring Opening

Grytsai,

Hamouda‐Tekaya,

Botton

et al. 2024

ChemMedChem

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Amidinoureas are an understudied class of molecules with unique structural properties and biological activities. A simple methodology has been developed for the synthesis of aliphatic substituted amidinoureas via unexpected cycle opening of benzothiazolo‐1,3,5‐triazine‐2‐ones and transamination reaction of N‐(N‐(benzo[d]thiazol‐2‐yl)carbamimidoyl)aniline‐1‐carboxamide in good yields. A novel series of amidinoureas derivatives was designed, synthesized, and evaluated for its antiproliferative activity on an aggressive metastatic melanoma A375 cell line model. This evaluation reveals antiproliferative activities in the low micromolar range and establishes a first structure‐activity relationship. In addition, analogues selected for their structural diversity were assayed on a panel of cancer cell lines through the DTP‐NCI60, on which they showed effectiveness on various cancer types, with promising activities on melanoma cells for two hit compounds. This work paves the way for further optimization of this family of compounds towards the development of potent antimelanoma agents.

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Synthesis and Biological Evaluation of Amidinourea Derivatives against Herpes Simplex Viruses

Cited by 8 publications

References 27 publications

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

A Systematic Review of Second-Line Treatments in Antiviral Resistant Strains of HSV-1, HSV-2, and VZV

Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5‐Triazin‐2‐one Ring Opening

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