Synthesis and in–vitro anti–HIV–1 evaluation of novel pyrazolo[4,3–c]pyridin–4–one derivatives

Kumar, Sanjay; Gupta, Shiv Shankar; Abadi, Leila Fotooh; Gaikwad, Shraddha; Desai, Dipen; Bhutani, K. K.; Kulkarni, Smita; Singh, Inder Pal

doi:10.1016/j.ejmech.2019.111714

Cited by 25 publications

(4 citation statements)

References 35 publications

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“…In addition, we deployed PBMCs and MΦ cells to assess the long-term (typically, five days) impact of the preparations on the cell viability. These cells are the primary targets for the virus invasion and hence could mimic the in vivo scenario and help shed more light on the mechanisms underlying HIV infection [ 63 – 65 ]. The in vitro cell viability assay showed that CC 50 values had a trend, i.e., AuNP-TNF>AuNPs>TNF in TZM-bl, PBMCs, and MΦ cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept

et al. 2023

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Background The adoption of Antiretroviral Therapy (ART) substantially extends the life expectancy and quality of HIV-infected patients. Yet, eliminating the latent reservoirs of HIV to achieve a cure remains an unmet need. The advent of nanomedicine has revolutionized the treatment of HIV/AIDS. The present study explores a unique combination of Tenofovir (TNF) with gold nanoparticles (AuNPs) as a potential therapeutic approach to overcome several limitations of the current ART. Results TNF-tethered AuNPs were successfully synthesized. Cell viability, genotoxicity, haemolysis, and histopathological studies confirmed the complete safety of the preparation. Most importantly, its anti-HIV1 reverse transcriptase activity was ~ 15 folds higher than the native TNF. In addition, it exhibited potent anti-HIV1 protease activity, a much sought-after target in anti-HIV1 therapeutics. Finally, the in vivo biodistribution studies validated that the AuNPs could reach many tissues/organs, serving as a secure nest for HIV and overcoming the problem of deficient drug delivery to HIV reservoirs. Conclusions We show that the combination of TNF and AuNPs exhibits multifunctional activity, viz. anti-HIV1 and anti-HIV1 protease. These findings are being reported for the first time and highlight the prospects of developing AuNP-TNF as a novel next-generation platform to treat HIV/AIDS. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept

et al. 2023

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“…A reference compound, standard diosgenin (Sigma Aldrich, MO, USA) were tested in each set of experiments for the comparative study. The methodology for these experiments was adopted from our earlier research work on this topic, with minor changes in the experimental setup [ [30] , [31] , [32] , [33] , [34] , [35] ].…”

Section: Methodsmentioning

confidence: 99%

Role of diosgenin extracted from Helicteres isora L in suppression of HIV-1 replication: An in vitro preclinical study

Rakshit,

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Gaikwad

et al. 2024

Heliyon

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“…The excess of lithiated base (either MeLi or LDA) may be at the origin of this alkylation, occurring most probably before the rearrangement of 16 (Scheme 6). 1 Looking for alternative methods for the preparation of aldehyde 12b, we planned then to reduce 3cyanopyridines 18 (also called nicotinonitriles) with diisobutylaluminum hydride (DIBALÀ H), [24] prepared itself by nucleophilic substitution of 2-chloro-3-cyanopyridine (Scheme 7). [25] The reduction reaction was performed with synthesized 2-benzyloxy and 2-(4methoxybenzyloxy) (PMBO) pyridine derivatives 18a and 18b and thus provided the corresponding aldehydes 12b and 12c with moderate to good yields (Scheme 7).…”

Section: Preparation Of C(2)-substituted Azaindolesmentioning

confidence: 99%

A Journey through Hemetsberger–Knittel, Leimgruber–Batcho and Bartoli Reactions: Access to Several Hydroxy 5‐ and 6‐Azaindoles

Radix

Hallé

Mahiout

et al. 2022

Helvetica Chimica Acta

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This work is dedicated to Prof. E. Peter Kündig for his 75th birthday and for his mentorship for three of us (S. R., Z. M. and T. L.) when we were post-doctoral research assistants in his laboratory.The preparation of various 5-and 6-azaindoles, heterocyclic structures that are frequently part of molecules in clinical development, and their monohydroxy analogues were described. Different strategies, relying on the de novo pyrrole ring formation, were investigated and, thanks to Hemetsberger-Knittel, Bartoli and Leimgruber-Batcho approaches, 4-and 7-monohydroxy 5-and 6-azaindoles were obtained. The crucial introduction of the oxygen atom was carried out from halogen derivatives, using nucleophilic substitution reactions under basic conditions with or without a copper catalyst. Some preliminary oxidation reactions have shown that it was yet not possible to synthesize the azaquinone indole structure from monohydroxy azaindole, using molecular oxygen in the presence of salcomine as a catalyst.

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Synthesis and in–vitro anti–HIV–1 evaluation of novel pyrazolo[4,3–c]pyridin–4–one derivatives

Cited by 25 publications

References 35 publications

Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept

Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept

Role of diosgenin extracted from Helicteres isora L in suppression of HIV-1 replication: An in vitro preclinical study

A Journey through Hemetsberger–Knittel, Leimgruber–Batcho and Bartoli Reactions: Access to Several Hydroxy 5‐ and 6‐Azaindoles

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