Docking and 3-D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-Nucleoside Binding Site and Design of Highly Active <i>N</i>-(2-Hydroxyethyl)carboxamide and <i>N</i>-(2-Hydroxyethyl)carbohydrazide Derivatives

Ragno, Rino; Artico, M.; Martino, Gabriella; Regina, Giuseppe La; Coluccia, Antonio; Pasquali, and Alessandra Di; Silvestri, Romano

doi:10.1021/jm040854k

Cited by 74 publications

(69 citation statements)

References 41 publications

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“…Overall, the compounds with an electron-withdrawing group on the phenyl ring exhibited excellent inhibition (entries 3-9). The same trend was observed when the substitution occurred at the 6-position of the phenyl ring (entries [13][14][15][16][17]. Exhilaratingly, the compounds with an electron-donating group on the same position provided superior inhibitory activity to the corresponding indolealkyl trifluoropyruvate derivatives (entries [10][11][12].…”

Section: Structure-activity Relationship (Sar) Studiessupporting

confidence: 60%

Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Han

Wang

et al. 2014

Org. Biomol. Chem.

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A series of non-nucleoside reverse transcriptase inhibitors derived from indole-based α-amino acids were designed and synthesized. Their inhibitory activities were detected by a TZM-bl cell assay on HIV virus type HIV-1IIIB. The comprehensive understanding of the SAR was obtained by utilizing the variation of the substituents of the indole-based α-amino acids. From the screened compounds, the novel inhibitors 19 and 29 were identified to be highly potent candidates with EC50 values of 0.060 μM and 0.045 μM respectively (CC50 values of 109.545 μM and 49.295 μM and SI values of 1825.8 and 1095.4). In most cases, the variation of substituents at different positions had a significant effect on the potency of activities. The results also indicate that the indole-based α-amino acids as efficient NNRTIs displayed comparable anti-HIV-1 activities to the reference drug NVP. We hope the identification of these indole-based amino acids as efficient NNRTIs of RT could stimulate researchers to develop more diversified anti-HIV drugs.

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Section: Structure-activity Relationship (Sar) Studiessupporting

confidence: 60%

Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Han

Wang

et al. 2014

Org. Biomol. Chem.

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“…The binding mode of compound 11 into the NNBS was analysed by means of a cross-docking procedure using 14 experimentally determined 3D structures of wild-type RT [51]. In all cases the docked conformations were in good agreement with each other.…”

Section: Binding Mode Analysis Through Docking Studiesmentioning

confidence: 99%

Indolyl aryl sulphones as HIV-1 reverse transcriptase inhibitors: docking and 3D QSAR studies

Ragno

Coluccia

Regina

et al. 2007

Expert Opinion on Drug Discovery

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Indolyl aryl sulphones (IASs) are a potent class of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) developed from early studies on pyrryl aryl sulphones and pyrrolobenzothiadiazepines and correlated with Merck's compound L-737,126. This review focuses on how molecular modelling studies, refined structure-based drug design (SBDD) and ligand-based drug design (LBDD) guided the activity prediction, synthesis and biological evaluation of new potent and selective IASs. In particular, the binding mode analysis (SBDD) and three-dimensional quantitative structure-activity relationship (3D QSAR) models (LBDD) are discussed, and their use is elucidated in design projects. Both SBDD and LBDD studies have led to the disclosure of subnanomolar active compounds. These compounds are revealed to be active against the most clinically relevant HIV-1 mutant strains and some drug-resistant clinical-isolated strains.

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“…The indole derivatives are known to possess anticancer, antioxidant, antitumor, and anti-HIV [8][9][10][11]28] activities.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Benzodiazepines Bearing Benzimidazole/Benzothiazole and Indole Moieties as a Potent Antimicrobial and Antioxidant Agents

Naraboli

Biradar

2018

Asian J Pharm Clin Res

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Objective: The present work deals with the synthesis and characterization of biologically active new indole derivatives, namely, 2-Methods: All these newly synthesized compounds were screened for their in vitro antimicrobial activity by an agar plate diffusion method, antioxidant activities such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), radical scavenging activity (RSA), ferric ions (Fe Result:The structures of all the newly synthesized compounds were characterized by their infrared, 1 H nuclear magnetic resonance, mass spectral studies, and elemental analysis. Compounds 7a and 7b exhibited good RSA at a concentration 100 µg/ml, compounds 6d, 7a-d and 8a-c displayed good FRAP at a concentration 100 µg/ml, compounds 7b-d and 8b-d showed good Fe 2+ ion metal chelating activity. Compounds 6b, 6d, 7a-d, and 8a-d exhibited good activity against all the screened bacteria and fungi.Conclusion: Some of the compounds have shown potent antimicrobial activity against all the screened bacteria and fungi, and some have exhibited very good antioxidant activity.

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Docking and 3-D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-Nucleoside Binding Site and Design of Highly Active N-(2-Hydroxyethyl)carboxamide and N-(2-Hydroxyethyl)carbohydrazide Derivatives

Cited by 74 publications

References 41 publications

Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Indolyl aryl sulphones as HIV-1 reverse transcriptase inhibitors: docking and 3D QSAR studies

Design and Synthesis of Benzodiazepines Bearing Benzimidazole/Benzothiazole and Indole Moieties as a Potent Antimicrobial and Antioxidant Agents

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