Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41

Shibo Jiang; Srinivasa R. Tala; Hong Lu; Peng Zou; Ilker Avan; Tarek S. Ibrahim; Nader E. Abo-Dya; Abdelmotaal Abdelmajeid; Asim K. Debnath; Alan R. Katritzky

doi:10.1016/j.bmcl.2011.08.081

Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41

Shibo Jiang, Srinivasa R. Tala, Hong Lu, Peng Zou, Ilker Avan, Tarek S. Ibrahim, Nader E. Abo-Dya, Abdelmotaal Abdelmajeid, Asim K. Debnath, Alan R. Katritzky

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Based on molecular docking analysis of earlier results, we designed a series of 2,5-disubstituted furans/pyrroles (5a-h) as HIV-1 entry inhibitors. Compounds were synthesized by Suzuki-Miyaura cross coupling, followed by a Knoevenagel condensation or Wittig reaction. Four of these compounds were found to be effective in inhibiting HIV-1 infection, with the best compounds being 5f and 5h, which exhibited significant inhibition on HIV-1 _IIIB infection at micromolar levels with low cytotoxicity. These compounds are also effective in blocking HIV-1 mediated cell-cell fusion and the gp41 six-helix bundle formation, suggesting that they are also HIV-1 fusion inhibitors targeting gp41 and have potential to be developed as a new class of anti-HIV-1 agents.

Original language	English (US)
Pages (from-to)	6895-6898
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2011.08.081
State	Published - Nov 15 2011

Bibliographical note

Funding Information:
We thank the University of Florida, The Kenan Foundation and King Abdulaziz University, Jeddah, Saudi Arabia for financial support. This study was supported by NIH grant AI046221 . We thank Dr. C. D. Hall for helpful discussions.

Keywords

ELISA
Furans
Gp41
HIV-1 fusion inhibitors
Pyrroles

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2011.08.081

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Jiang, S., Tala, S. R., Lu, H., Zou, P., Avan, I., Ibrahim, T. S., Abo-Dya, N. E., Abdelmajeid, A., Debnath, A. K., & Katritzky, A. R. (2011). Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41. Bioorganic and Medicinal Chemistry Letters, 21(22), 6895-6898. https://doi.org/10.1016/j.bmcl.2011.08.081

Jiang, S, Tala, SR, Lu, H, Zou, P, Avan, I, Ibrahim, TS, Abo-Dya, NE, Abdelmajeid, A, Debnath, AK & Katritzky, AR 2011, 'Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 22, pp. 6895-6898. https://doi.org/10.1016/j.bmcl.2011.08.081

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abstract = "Based on molecular docking analysis of earlier results, we designed a series of 2,5-disubstituted furans/pyrroles (5a-h) as HIV-1 entry inhibitors. Compounds were synthesized by Suzuki-Miyaura cross coupling, followed by a Knoevenagel condensation or Wittig reaction. Four of these compounds were found to be effective in inhibiting HIV-1 infection, with the best compounds being 5f and 5h, which exhibited significant inhibition on HIV-1 IIIB infection at micromolar levels with low cytotoxicity. These compounds are also effective in blocking HIV-1 mediated cell-cell fusion and the gp41 six-helix bundle formation, suggesting that they are also HIV-1 fusion inhibitors targeting gp41 and have potential to be developed as a new class of anti-HIV-1 agents.",

keywords = "ELISA, Furans, Gp41, HIV-1 fusion inhibitors, Pyrroles",

author = "Shibo Jiang and Tala, {Srinivasa R.} and Hong Lu and Peng Zou and Ilker Avan and Ibrahim, {Tarek S.} and Abo-Dya, {Nader E.} and Abdelmotaal Abdelmajeid and Debnath, {Asim K.} and Katritzky, {Alan R.}",

note = "Funding Information: We thank the University of Florida, The Kenan Foundation and King Abdulaziz University, Jeddah, Saudi Arabia for financial support. This study was supported by NIH grant AI046221 . We thank Dr. C. D. Hall for helpful discussions. ",

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AU - Zou, Peng

AU - Avan, Ilker

AU - Ibrahim, Tarek S.

AU - Abo-Dya, Nader E.

AU - Abdelmajeid, Abdelmotaal

AU - Debnath, Asim K.

AU - Katritzky, Alan R.

N1 - Funding Information: We thank the University of Florida, The Kenan Foundation and King Abdulaziz University, Jeddah, Saudi Arabia for financial support. This study was supported by NIH grant AI046221 . We thank Dr. C. D. Hall for helpful discussions.

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Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

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