Searching for novel N 1 -substituted benzimidazol-2-ones as non-nucleoside HIV-1 RT inhibitors

Ferro, Stefania; Buemi, Maria Rosa; Luca, Laura De; Agharbaoui, Fatima E.; Pannecouque, Christophe; Monforte, Anna Maria

doi:10.1016/j.bmc.2017.05.040

Cited by 20 publications

(13 citation statements)

References 24 publications

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“…While virtual screening of compounds that are active against mutant RT forms is not widely used, an application of molecular docking to virtual screening of compounds, active against wild-type of RT can be performed [ 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. Typically such studies provide some insights into intermolecular interactions affecting both wild-type and mutant enzymes.…”

Section: Resultsmentioning

confidence: 99%

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

2018

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Currently, millions of people are living with human immunodeficiency virus type 1 (HIV-1), which causes acquired immunodeficiency syndrome. However, the spread of the HIV-1 resistance to antiviral agents is the major problem in the antiretroviral therapy and medical management of HIV-infected patients. HIV-1 reverse transcriptase (RT) is one of the key viral targets for HIV-1 inhibition. Therefore, the studies on the combatting the HIV resistance that occurs due to the structural changes in RT, are in great demand. This work aims to provide an overview of the state-of-the-art molecular docking approaches applied to the studies of the HIV-1 resistance, associated with RT structure changes. We have reviewed recent studies using molecular docking with mutant forms of RT. The work discusses the modifications of molecular docking, which have been developed to find the novel molecules active against resistance mutants of RT and/or recombinant strains of HIV-1. The perspectives of the existing algorithms of molecular docking to the studies on molecular mechanisms of resistance and selection of the correct binding poses for the reverse transcriptase inhibitors are discussed.

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Section: Resultsmentioning

confidence: 99%

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

2018

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“…Characterization of each new intermediate and final compound (i.e. melting points, elemental analyses and NMR spectra) were determined by means of equipments previously reported by our group, as well as materials and purification methods …”

Section: Methodsmentioning

confidence: 99%

“…Derivatives 10 – 12 were prepared following the synthetic procedures previously reported by us . A mixture of anhydrous sodium hydride (5 mmol) and 2‐nitroaniline (138 mg, 1 mmol) or 5‐chloro‐2‐nitroaniline (173 mg, 1 mmol) in DMF (5 ml) was stirred for 10 min at 0°C and then 3,5‐dimethylbenzyl bromide (597 mg, 3 mmol) or 3,5‐dimethylbenzensulphonyl chloride (614 mg, 3 mmol) was added.…”

Section: Methodsmentioning

confidence: 99%

“…Derivatives 13 – 15 were prepared following the synthetic procedures previously reported by us . The mixture of N ‐substituted‐2‐nitroanilines (1 mmol) or N ‐(2‐nitrophenyl)‐benzenesulfonamides (1 mmol) in HCl conc.…”

Section: Methodsmentioning

confidence: 99%

“…Derivatives 16 – 18 were prepared following the synthetic procedures previously reported by us . To a solution of N 1 ‐(substituted‐benzyl)‐2‐amino aniline (1 mmol) or N ‐(2‐aminophenyl)‐benzenesulfonamides (1 mmol) in pyridine (10 ml) 1,1′‐thiocarbonyldiimidazole (250 mg, 1.4 mmol) was added at room temperature and the resulting mixture was maintained under stirring for 1 hr.…”

Section: Methodsmentioning

confidence: 99%

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Discovery of benzimidazole‐based Leishmania mexicana cysteine protease CPB2.8ΔCTE inhibitors as potential therapeutics for leishmaniasis

et al. 2018

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Chemotherapy is currently the only effective approach to treat all forms of leishmaniasis. However, its effectiveness is severely limited due to high toxicity, long treatment length, drug resistance, or inadequate mode of administration. As a consequence, there is a need to identify new molecular scaffolds and targets as potential therapeutics for the treatment of this disease. We report a small series of 1,2-substituted-1H-benzo[d]imidazole derivatives (9a-d) showing affinity in the submicromolar range (K = 0.15-0.69 μM) toward Leishmania mexicanaCPB2.8ΔCTE, one of the more promising targets for antileishmanial drug design. The compounds confirmed activity in vitro against intracellular amastigotes of Leishmania infantum with the best result being obtained with derivative 9d (IC = 6.8 μM), although with some degree of cytotoxicity (CC = 8.0 μM on PMM and CC = 32.0 μM on MCR-5). In silico molecular docking studies and ADME-Tox properties prediction were performed to validate the hypothesis of the interaction with the intended target and to assess the drug-likeness of these derivatives.

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Deciphering the enigmas of non‐nucleoside reverse transcriptase inhibitors (NNRTIs): A medicinal chemistry expedition towards combating HIV drug resistance

Zhang,

et al. 2024

Medicinal Research Reviews

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The pivotal involvement of reverse transcriptase activity in the pathogenesis of the progressive HIV virus has stimulated gradual advancements in drug discovery initiatives spanning three decades. Consequently, nonnucleoside reverse transcriptase inhibitors (NNRTIs) have emerged as a preeminent category of therapeutic agents for HIV management. Academic institutions and pharmaceutical companies have developed numerous NNRTIs, an essential component of antiretroviral therapy. Six NNRTIs have received Food and Drug Administration approval and are widely used in clinical practice, significantly improving the quality of HIV patients. However, the rapid emergence of drug resistance has limited the effectiveness of these medications, underscoring the necessity for perpetual research and development of novel therapeutic alternatives. To supplement the existing literatures on NNRTIs, a comprehensive review has been compiled to synthesize this extensive dataset into a comprehensible format for the medicinal chemistry community. In this review, a thorough investigation and meticulous analysis were conducted on the progressions achieved in NNRTIs within the past 8 years (2016–2023), and the experiences and insights gained in the development of inhibitors with varying chemical structures were also summarized. The provision of a crucial point of reference for the development of wide‐ranging anti‐HIV medications is anticipated.

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Searching for novel N 1 -substituted benzimidazol-2-ones as non-nucleoside HIV-1 RT inhibitors

Cited by 20 publications

References 24 publications

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

Discovery of benzimidazole‐based Leishmania mexicana cysteine protease CPB2.8ΔCTE inhibitors as potential therapeutics for leishmaniasis

Deciphering the enigmas of non‐nucleoside reverse transcriptase inhibitors (NNRTIs): A medicinal chemistry expedition towards combating HIV drug resistance

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