Design, discovery, modelling, synthesis, and biological evaluation of novel and small, low toxicity s-triazine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors

Viira, Birgit; Selyutina, Anastasia; García-Sosa, Alfonso T.; Karonen, Maarit; Sinkkonen, Jari; Merits, Andres; Maran, Uko

doi:10.1016/j.bmc.2016.04.018

Cited by 33 publications

(36 citation statements)

References 57 publications

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“…For production of HIV-1, 6 × 10 6 ACH-2 cells were seeded in 10 mL of full culture media, and HIV-1 production was induced by the addition of 100 nM phorbol 12-myristate 13-acetate (Viira et al, 2016). The induced cells were incubated for 48 h, and subsequently, the HIV-1 containing media was collected and filtered.…”

Section: Virusesmentioning

confidence: 99%

Novel activities of safe-in-human broad-spectrum antiviral agents

et al. 2018

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According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.

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Section: Virusesmentioning

confidence: 99%

Novel activities of safe-in-human broad-spectrum antiviral agents

et al. 2018

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“…In the experimental evaluation of selected compounds, a diaryltriazine (DATA) directly inhibited the HIV RT, displayed antiviral activity in a virus like particle‐based assay and presented no cytotoxicity. A series of derivatives were synthesized resulting in a compound with an EC 50 of 160 nM against HIV‐1 WT ( 59 ) …”

Section: Drug Design Strategiesmentioning

confidence: 99%

“…A series of derivatives were synthesized resulting in a compound with an EC 50 of 160 nM against HIV-1 WT (59). 75 To take into account the flexibility of the NNIBP, Ivetac et al 76 adopted an ensemble-based virtual screening strategy. In a hierarchical protocol, they first docked compounds from the NCI database into 10 diverse crystal In close relationship with the flexibility of the NNIBP, the shape of the binding pocket and the interaction pattern with the inhibitor varies for different NNRTIs.…”

Section: Structure-based Virtual Screeningmentioning

confidence: 99%

Challenges and approaches in the discovery of human immunodeficiency virus type‐1 non‐nucleoside reverse transcriptase inhibitors

Battini

Bollini

2018

Medicinal Research Reviews

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The type I human immunodeficiency virus (HIV‐1) pandemic affecting over 37 million people worldwide continues, with 1.8 million people newly infected each year. Highly active antiretroviral therapy is efficient at reducing viral load and nearly one‐half of the infected population is on treatment. One of the most successful approaches for the treatment of HIV infections is the use of inhibitors for human immunodeficiency virus type‐1 reverse transcriptase (HIV‐1 RT). At present, there are six nonnucleoside reverse transcriptase inhibitors (NNRTIs) approved for clinical use: nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETV), rilpivirine (RPV), and elsulfavirine. In this review, we will cover the development of different classes of NNRTIs over the last two decades. We will give an overview of traditional medicinal chemistry strategies for structural modification as bioisosterism principles, scaffold hopping, substitute decoration, and molecular hybridization. Furthermore, computer‐aid design as virtual screening, de novo design and free‐energy perturbation will be described in details.

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“…Considering the immensely rich diverse biological properties of s ‐triazine , imidazoles , and benzimidazoles , it was found of paramount interest to incorporate all these biologically active privileged pharmacophores into a single molecular framework by utilizing the reactivity of an active synthon imidate ester (Fig. ).…”

Section: Introductionmentioning

confidence: 99%