Structural optimization of pyridine-type DAPY derivatives to exploit the tolerant regions of the NNRTI binding pocket

Chen, Wenmin; Zhan, Peng; Daelemans, Dirk; Yang, Jiapei; Huang, Boshi; Clercq, Erik De; Pannecouque, Christophe; Liu, Xinyong

doi:10.1016/j.ejmech.2016.05.054

Cited by 26 publications

(24 citation statements)

References 40 publications

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“…Indeed, E138K and K103N are known as the major ones among the existing mutations [66]. Hence, finding and improving new NNRTIs with good efficacy against resistant mutations can be a controversial subject in the field of biomedical chemistry [67].…”

Section: Anti-hiv Effects Of Thiophenementioning

confidence: 99%

Recent Advancements in Polythiophene-Based Materials and their Biomedical, Geno Sensor and DNA Detection

Mousavi

Hashemi

Bahrani

et al. 2021

IJMS

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In this review, the unique properties of intrinsically conducting polymer (ICP) in biomedical engineering fields are summarized. Polythiophene and its valuable derivatives are known as potent materials that can broadly be applied in biosensors, DNA, and gene delivery applications. Moreover, this material plays a basic role in curing and promoting anti-HIV drugs. Some of the thiophene’s derivatives were chosen for different experiments and investigations to study their behavior and effects while binding with different materials and establishing new compounds. Many methods were considered for electrode coating and the conversion of thiophene to different monomers to improve their functions and to use them for a new generation of novel medical usages. It is believed that polythiophenes and their derivatives can be used in the future as a substitute for many old-fashioned ways of creating chemical biosensors polymeric materials and also drugs with lower side effects yet having a more effective response. It can be noted that syncing biochemistry with biomedical engineering will lead to a new generation of science, especially one that involves high-efficiency polymers. Therefore, since polythiophene can be customized with many derivatives, some of the novel combinations are covered in this review.

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Section: Anti-hiv Effects Of Thiophenementioning

confidence: 99%

Recent Advancements in Polythiophene-Based Materials and their Biomedical, Geno Sensor and DNA Detection

Mousavi

Hashemi

Bahrani

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…The typically different solubilities of compounds 76 (pH 7.0, S > 48 μg/ml), 77 (pH 7.0, S > 56 μg/ml) and 78 (pH 7.0, S > 11 μg/ml) (Table 9 and Figure 22) were observed and the paranocyananiline fragment was suspected as a key point of solubility. Predicted by the molecular docking, the incorporated morpholinyl or piperidyl group was extended into the deeper solvent‐protein region of NNIBP (Figure 22), potentially making the molecules more water soluble 104 . This strategy was also used for improving drug resistance properties and PK profiles 56 .…”

Section: Improvement Of Pk Profilesmentioning

confidence: 99%

Druggability modification strategies of the diarylpyrimidine‐type non‐nucleoside reverse transcriptase inhibitors

Zhuang

Chen

2021

Medicinal Research Reviews

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Drug discovery of human immunodeficiency virus (HIV) is a hot field in medicinal chemistry community for many years. The diarylpyrimidines (DAPYs) are the second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTIs) targeting reverse transcriptase, playing a great irreplaceable role in HIV transcriptional therapy. However, fast‐growing drug‐resistant mutations as nonnegligible challenge are still unpredictably appeared in the clinical practice, leading to deactivate or reduce the existing drugs. In the last 20 years, more and more novel DAPY derivatives have developed with the purpose to counter the mutants. Nevertheless, most of them have dissatisfactory pharmacokinetics (PK) or poor antiviral activity toward resistant mutant strains. In this article, we will analyze the NNRTI derivatives with promising druggability, and summarize a series of druggability modification strategies to improve the antiviral activity, reduce toxicity and improve the PK properties in recent years. The prospects of DAPYs and the directions for future efforts will be discussed.

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“…Several other examples of DAPY derivatives which explore the tolerant region II have been recently reported (Figure ). Most of the derivatives had higher water solubility and proved to be highly effective in inhibiting HIV‐1 replication at nanomolar concentrations …”

Section: Drug Design Strategiesmentioning

confidence: 99%

“…Most of the derivatives had higher water solubility and proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. 13,22,[108][109][110] Another successful strategy was the introduction of biphenyl derivatives on the left wing of DAPYs to bind the hydrophobic region in the NNIBP. Molecular modeling studies have indicated that the molecules bind the NNIBP in a "U" shape, similarly to most of the other DAPYs.…”

Section: Traditional Medicinal Chemistry Approachmentioning

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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Structural optimization of pyridine-type DAPY derivatives to exploit the tolerant regions of the NNRTI binding pocket

Cited by 26 publications

References 40 publications

Recent Advancements in Polythiophene-Based Materials and their Biomedical, Geno Sensor and DNA Detection

Recent Advancements in Polythiophene-Based Materials and their Biomedical, Geno Sensor and DNA Detection

Druggability modification strategies of the diarylpyrimidine‐type non‐nucleoside reverse transcriptase inhibitors

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

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