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

Battini, Leandro; Bollini, Mariela

doi:10.1002/med.21544

Cited by 42 publications

(27 citation statements)

References 144 publications

(261 reference statements)

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“…The flexibility allows these NNRTIs to tolerate these single-point mutations ( Wang et al, 2020 ). However, emergence of double mutations caused resistance to the second and the third generation NNRTIs ( Battini and Bollini, 2019 ). Therefore, new inhibitors with better structural adaptability are required to overcome this problem.…”

Section: Introductionmentioning

confidence: 99%

Anti-HIV-1 reverse transcriptase property of some edible mushrooms in Asia

Choengpanya

Ratanabunyong

Seetaha

et al. 2021

Saudi Journal of Biological Sciences

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Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), which is a serious health threat worldwide. One of its core enzymes, reverse transcriptase (RT), is a target for HIV inhibition. A number of bioactive compounds have been successfully used for HIV treatment. However, HIV rapidly mutates, and long-term treatment can cause drug-resistant strains. Therefore, new inhibitors are required to overcome this problem. In this study, the aqueous, ethanolic and hexane crude extracts of 19 edible and medicinal mushrooms, which are widely grown and available commercially in Thailand, were screened against HIV-1 RT. The results showed that the water extracts of A. blazei and I. obliquus , the ethanol extracts of I. obliquus and P. igniarius and the hexane extract of I. obliquus exhibited strong anti-HIV-1 RT activity with IC 50 values of 1.92 ± 0.15, 4.39 ± 0.79, 6.17 ± 0.76 and 7.75 ± 246 µg/ml, respectively. These mushrooms have the potential for HIV treatment, and further study on identification of the bioactive compounds against HIV-1 RT should be performed.

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Section: Introductionmentioning

confidence: 99%

Anti-HIV-1 reverse transcriptase property of some edible mushrooms in Asia

Choengpanya

Ratanabunyong

Seetaha

et al. 2021

Saudi Journal of Biological Sciences

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“…The main purpose of the design of HIV-1 inhibitors is to suppress the replication of HIV-1 in the long-term therapy and to maintain the function of the immune function [49]. Given that delavirdine [50] with indole 2-carboxamide skeletal is used to treat HIV-1, other indole 2-carboxamide derivatives have the potential to inhibit HIV-1 virus activity. It should be noted that many researchers have used nevirapine and efavirenz as the control to compare with indole 2-carboxamide derivatives (HIV-1 inhibition).…”

Section: Hiv-1 Entry Inhibitorsmentioning

confidence: 99%

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

Chehardoli

Bahmani

2020

Mol Divers

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Indole derivatives have been the focus of many researchers in the study of pharmaceutical compounds for many years. Researchers have investigated the effect of carboxamide moiety at positions 2 and 3, giving unique inhibitory properties to these compounds. The presence of carboxamide moiety in indole derivatives causes hydrogen bonds with a variety of enzymes and proteins, which in many cases, inhibits their activity. In this review, synthetic strategies of indole 2 and 3-carboxamide derivatives, the type, and mode of interaction of these derivatives against HLGP, HIV-1, renin enzyme, and structure-activity studies of these compounds were investigated. It is hoped that indole scaffolds will be tested in the future for maximum activity in pharmacological compounds.

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“…The flexibility between the aromatic rings, allowing the DAPYs to adopt multiple conformations of RT, is accounted for the potent activity against many resistant virus strains 8 . However, growing drug‐resistant mutations are still unavoidable appeared in the clinical practice of these two drugs 9 . The adverse effects and poor physicochemical properties also disturbed their clinical applications.…”

Section: Introductionmentioning

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

Cited by 42 publications

References 144 publications

Anti-HIV-1 reverse transcriptase property of some edible mushrooms in Asia

Anti-HIV-1 reverse transcriptase property of some edible mushrooms in Asia

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

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

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