Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

Makarasen, Arthit; Kuno, Mayuso; Patnin, Suwicha; Reuk-Ngam, Nanthawan; Khlaychan, Panita; Deeyohe, Sirinya; Intachote, Pakamas; Saimanee, Busakorn; Sengsai, Suchada; Boonsri, Pornthip; Chaivisuthangkura, Apinya; Sirithana, Wandee; Techasakul, Supanna

doi:10.1055/a-0968-1150

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…Molecular docking is a computational procedure that predicts the lowest energy binding conformations of one molecule to a second (usually a small drug-like molecule to a protein). Accordingly, molecular docking procedures, along with their different scoring systems, are frequently utilized to predict the binding modes and affinities between chemical compounds and drug binding sites on biological macromolecules [ 29 , 30 ].…”

Section: Computer-aided Drug Designmentioning

confidence: 99%

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Salman

Al-Obaidi

Kitchen

et al. 2021

IJMS

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Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.

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Section: Computer-aided Drug Designmentioning

confidence: 99%

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Salman

Al-Obaidi

Kitchen

et al. 2021

IJMS

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“…Compound 51 reduced HIV‐1 RT to the same extent as control drug NVP. The cytotoxicity against MOLT‐3 (acute lymphoblastic leukemia) was robust, with an IC 50 of 4.63 μM which was similar to EFV and TMC278 [101] …”

Section: Role Of Nitrogen‐containing Heterocyclic Compounds In Inhibi...mentioning

confidence: 91%

“…The cytotoxicity against MOLT-3 (acute lymphoblastic leukemia) was robust, with an IC 50 of 4.63 μM which was similar to EFV and TMC278. [101] Romeo and co-workers reported a class of pyrimidinones with an isoxazolidine nucleus as anti-HIV therapeutics. Compounds with ether functional groups at C-3 emerged as potent NNRTIs.…”

Section: Chemistryselectmentioning

confidence: 99%

Recent Advances on the Role of Nitrogen‐Based Heterocyclic Scaffolds in Targeting HIV through Reverse Transcriptase Inhibition

Kumar¹,

Wahan²,

Virendra³

et al. 2022

ChemistrySelect

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Acquired immune deficiency syndrome (AIDS) caused by human immunodeficiency virus continues to scavenge lives of millions around the world. Reverse transcriptase (RT) also known as the RNA-directed DNA polymerase enzyme is responsible for converting RNA into viral DNA through process known as reverse transcription. Investigations on the pathogenic aspects of the RT enzyme, its associated elements such as gag (group-specific antigen gene), pol (polymerase gene), and env (environmental gene) (envelope gene) reveals its contribution towards emergence of resistance to all various anti-HIV drugs. Therefore, research into the control and blockage of the RT pathway has been a prominent focus in the quest for novel targets for HIV treatment. A slew of heterocyclics has been claimed to play a significant part in the fight against doomy HIV, saving the lives of millions of people throughout the world and providing hope for HIV treatment. Due to their improved potency and selectivity, as well as the fact that they have fewer off-target effects against the several targets implicated in RT inhibition, heterocyclics are becoming more and more useful. The RT inhibition pathway, the function of numerous heterocyclic scaffolds, and their ability to inhibit the RT enzyme pathway have all been the main topics of this paper. Recent advances in RT inhibitors in the last eight years (2014-2022) including mechanisms of action, preclinical and clinical investigations, structural activity relationships, and docking studies, to investigate mechanistic studies that would eventually aid in the design and development of powerful RT inhibitors have also discussed.

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“…The interaction of (2) in the binding pocket of HIV-1 RT was similar to that of NVP, EFV, and RPV because those ligands performed two conventional hydrogen bonds with LYS101. In addition, compounds (1) and ( 2) have also been examined for HIV-1 RT inhibiting activity and exhibited inhibition rates of 25.46% and 27.85% at 1 µM concentration, respectively [19,20]. Therefore, 4-(2′,6′-dimethyl-4′-cyanophenoxy)-6-(4′′-cyanophenyl)-aminoquinoline (1) and 4-(2′,6′-dimethyl-4′cyanophenoxy)-2-(4′′-cyanophenyl)-aminoquinoline (2) will be utilized to develop new anti-HIV-1RT agents.…”

Section: Cross-docking Between Ligands With Hiv-1 Rtmentioning

confidence: 99%

Design, cross-docking and ONIOM studies of potent antiviral HIV-1 nonnucleoside reverse transcriptase inhibitors

Patnin,

Makarasen,

Vijitphan

et al. 2023

Preprint

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In the present study, we aimed to develop and discover anti-HIV-1 reverse transcriptase (RT) using quinoline as a core structure. Quinoline derivatives were designed using a molecular hybridization approach through the fusion of the pharmacophores present in the structures of HIV-1 RT drugs, namely, nevirapine, efavirenz, etravirine, talviraline, and rilpivirine. Quinoline derivatives were developed into two compounds, namely,4-(2′,6′-dimethyl-4′-cyanophenoxy)-6-(4′′-cyanophenyl)-aminoquinoline (1) and 4-(2′,6′-dimethyl-4′-cyanophenoxy)-2-(4′′-cyanophenyl)-aminoquinoline (2). The binding interactions between nonnucleoside reverse transcriptase inhibitors (NNRTIs), quinoline derivatives and HIV-1 RT were investigated using cross-docking, molecular docking and the ONIOM approach. The cross-docking showed that the conformation of 4G1Q.pdb had the lowest binding energy values compared with the other conformations of HIV-1 RT. The molecular docking and ONIOM results revealed that (2) interacted with LYS101 residues through hydrogen bonding and interacted with TYR181 and TRP229 residues through pi–pi stacking in the binding pocket of HIV-1 RT, similar to that of rilpivirine. Moreover, (2) and rilpivirine had the lowest total interaction energy compared with other ligands. Therefore, the design and development of 2-amino-4-phenoxy-substituted quinoline as an inhibitor of HIV-1 RT is of interest for further study. The data suggested that these novel series could serve as a starting point for the development of anti-HIV-1 drugs in the near future.

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Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

Cited by 10 publications

References 30 publications

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Recent Advances on the Role of Nitrogen‐Based Heterocyclic Scaffolds in Targeting HIV through Reverse Transcriptase Inhibition

Design, cross-docking and ONIOM studies of potent antiviral HIV-1 nonnucleoside reverse transcriptase inhibitors

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