scholarly journals New developments in anti-HIV chemotherapy

2001 ◽  
Vol 73 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Erik De Clercq
Keyword(s):  
Reverse Transcriptase ◽  
Viral Entry ◽  
Hiv Infections ◽  
Viral Envelope ◽  
Reverse Transcriptase Inhibitors ◽  
Intact Cells ◽  
Metabolic Characteristics ◽  
Glycoprotein Gp120 ◽  
Anti Hiv Agents ◽  
Anti Hiv

Virtually all the compounds that are currently used, or under advanced clinical trial, for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir (PMPA), and disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, and emivirine; and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir. In addition, various other events in the HIV replicative cycle are potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120; (ii) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5; (iii) virus-cell fusion; (iv) viral assembly and disassembly; (v) proviral DNA integration; and (vi) viral mRNA transcription. Also, new NRTIs, NNRTIs, and PIs have been developed that possess respectively improved metabolic characteristics, or increased activity against NNRTI-resistant HIV strains or, as in the case of PIs, a different, nonpeptidic scaffold. Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating from cell-free enzymatic assays to the mode of action of these agents in intact cells.

New Perspectives for the Treatment of HIV Infections

1998 ◽  
Vol 63 (4) ◽  
pp. 449-479 ◽  
Author(s):  
Erik De Clercq
Keyword(s):  
Reverse Transcriptase ◽  
Binding Site ◽  
Substrate Binding ◽  
Hiv Infections ◽  
Reverse Transcriptase Inhibitors ◽  
Substrate Binding Site ◽  
Hiv Inhibition ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Replicative Cycle

The HIV replicative cycle reveals several virus-specific events that could function as targets for chemotherapeutic intervention. The compounds that are presently available as anti-HIV drugs are targeted at either the substrate binding site of the reverse transcriptase (zidovudine, didanosine, zalcitabine, stavudine, lamivudine) or a non-substrate binding site of the reverse transcriptase (nevirapine, delavirdine), or the viral protease (saquinavir, ritonavir, indinavir, nelfinavir). Remarkable clinical efficacy has been observed with combinations of different reverse transcriptase inhibitors and protease inhibitors. It may be anticipated that with the advent of newer and more efficient compounds the effectiveness of HIV inhibition could still be improved upon and the prospects for a definitive cure of the disease may be accomplished. An account with 107 references.

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

Drug Research ◽  
2019 ◽  
Vol 69 (12) ◽  
pp. 671-682 ◽  
Author(s):  
Arthit Makarasen ◽  
Mayuso Kuno ◽  
Suwicha Patnin ◽  
Nanthawan Reukngam ◽  
Panita Khlaychan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Reverse Transcriptase ◽  
Lymphoblastic Leukemia ◽  
Docking Studies ◽  
Elisa Method ◽  
Reverse Transcriptase Inhibitors ◽  
Anti Hiv Agents ◽  
Near Future ◽  
Anti Hiv ◽  
Hiv 1

AbstractIn this study, amino-oxy-diarylquinolines were designed using structure-guided molecular hybridization strategy and fusing of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), etravirine (ETV, TMC125) and rilpivirine (RPV, TMC278). The anti-HIV-1 reverse transcriptase (RT) activity was evaluated using standard ELISA method, and the cytotoxic activity was performed using MTT and XTT assays. The primary bioassay results indicated that 2-amino-4-oxy-diarylquinolines possess moderate inhibitory properties against HIV-1 RT. Molecular docking results showed that 2-amino-4-oxy-diarylquinolines 8(a-d) interacted with the Lys101 and His235 residue though hydrogen bonding and interacted with Tyr318 residue though π-π stacking in HIV-1 RT. Furthermore, 8a and 8d were the most potent anti-HIV agents among the designed and synthesized compounds, and their inhibition rates were 34.0% and 39.7% at 1 µM concentration. Interestingly, 8a was highly cytotoxicity against MOLT-3 (acute lymphoblastic leukemia), with an IC50 of 4.63±0.62 µg/mL, which was similar with that in EFV and TMC278 (IC50 7.76±0.37 and 1.57±0.20 µg/ml, respectively). Therefore, these analogs of the synthesized compounds can serve as excellent bases for the development of new anti-HIV-1 agents in the near future.

New Alkenyldiarylmethanes with Enhanced Potencies as Anti-HIV Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors

1998 ◽  
Vol 41 (12) ◽  
pp. 2076-2089 ◽  
Author(s):  
Mark Cushman ◽  
Agustin Casimiro-Garcia ◽  
Elzbieta Hejchman ◽  
Jeffrey A. Ruell ◽  
Mingjun Huang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Anti Hiv Agents ◽  
Anti Hiv

Design, synthesis, and anti-HIV activity of 4′-modified carbocyclic nucleoside phosphonate reverse transcriptase inhibitors

2009 ◽  
Vol 17 (4) ◽  
pp. 1739-1746 ◽  
Author(s):  
Constantine G. Boojamra ◽  
Jay P. Parrish ◽  
David Sperandio ◽  
Ying Gao ◽  
Oleg V. Petrakovsky ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Reverse Transcriptase Inhibitors ◽  
Design Synthesis ◽  
Carbocyclic Nucleoside ◽  
Anti Hiv

scholarly journals Fullerene Derivatives of Nucleoside HIV Reverse Transcriptase Inhibitors—In Silico Activity Prediction

2018 ◽  
Vol 19 (10) ◽  
pp. 3231 ◽  
Author(s):  
Aleksandra Dąbrowska ◽  
Tomasz Pieńko ◽  
Przemysław Taciak ◽  
Katarzyna Wiktorska ◽  
Zdzisław Chilmonczyk ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Hiv Reverse Transcriptase ◽  
Reverse Transcriptase Inhibitors ◽  
Activity Prediction ◽  
Hiv Therapy ◽  
C20 Fullerene ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Similar Affinity ◽  
Hiv 1

Here we present new derivatives of nucleoside reverse transcriptase inhibitors with a C20 fullerene. The computational chemistry methods used in this study evaluate affinity of designed compounds towards the HIV-1 reverse transcriptase (RT) binding site and select the most active ones. The best of the designed compounds have superior or similar affinity to RT active site in comparison to most active test compounds, including drugs used in anti-HIV therapy.

The antiviral lectin cyanovirin-N: probing multivalency and glycan recognition through experimental and computational approaches

2013 ◽  
Vol 41 (5) ◽  
pp. 1170-1176 ◽  
Author(s):  
Brian W. Woodrum ◽  
Jason D. Maxwell ◽  
Ashini Bolia ◽  
S. Banu Ozkan ◽  
Giovanna Ghirlanda
Keyword(s):  
Viral Entry ◽  
High Specificity ◽  
Integrated Approach ◽  
Protein Gp120 ◽  
Computational Work ◽  
Gp120 Glycoprotein ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Envelope Protein Gp120

CVN (cyanovirin-N), a small lectin isolated from cyanobacteria, exemplifies a novel class of anti-HIV agents that act by binding to the highly glycosylated envelope protein gp120 (glycoprotein 120), resulting in inhibition of the crucial viral entry step. In the present review, we summarize recent work in our laboratory and others towards determining the crucial role of multivalency in the antiviral activity, and we discuss features that contribute to the high specificity and affinity for the glycan ligand observed in CVN. An integrated approach that encompasses structural determination, mutagenesis analysis and computational work holds particular promise to clarify aspects of the interactions between CVN and glycans.

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