Bioinspired Pyrano[2,3-<i>f</i>]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation
We have designed and synthesized a series of bioinspired pyrano[2,3-<i>f</i>]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Biomimetics |
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| Online Access: | https://www.mdpi.com/2313-7673/9/1/44 |
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| author | Igor A. Khalymbadzha Ramil F. Fatykhov Ilya I. Butorin Ainur D. Sharapov Anastasia P. Potapova Nibin Joy Muthipeedika Grigory V. Zyryanov Vsevolod V. Melekhin Maria D. Tokhtueva Sergey L. Deev Marina K. Kukhanova Nataliya N. Mochulskaya Mikhail V. Tsurkan |
| author_facet | Igor A. Khalymbadzha Ramil F. Fatykhov Ilya I. Butorin Ainur D. Sharapov Anastasia P. Potapova Nibin Joy Muthipeedika Grigory V. Zyryanov Vsevolod V. Melekhin Maria D. Tokhtueva Sergey L. Deev Marina K. Kukhanova Nataliya N. Mochulskaya Mikhail V. Tsurkan |
| author_sort | Igor A. Khalymbadzha |
| collection | DOAJ |
| description | We have designed and synthesized a series of bioinspired pyrano[2,3-<i>f</i>]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2<i>H</i>,8<i>H</i>-pyrano[2,3-<i>f</i>]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction. Antiviral assay of the synthesized compounds showed that compound <b>4</b> has moderate activity against HIV-1 on enzymes and poor activity on the cell model. A molecular docking study demonstrates a good correlation between in silico and in vitro HIV-1 reverse transcriptase (RT) activity of the compounds when docked to the nonnucleoside RT inhibitor binding site, and alternative binding modes of the considered analogs of Calanolide A were established. |
| first_indexed | 2024-03-08T11:04:42Z |
| format | Article |
| id | doaj.art-bb4f6881cd7241e0897dfbe5f9b17b6d |
| institution | Directory Open Access Journal |
| issn | 2313-7673 |
| language | English |
| last_indexed | 2024-03-08T11:04:42Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomimetics |
| spelling | doaj.art-bb4f6881cd7241e0897dfbe5f9b17b6d2024-01-26T15:16:25ZengMDPI AGBiomimetics2313-76732024-01-01914410.3390/biomimetics9010044Bioinspired Pyrano[2,3-<i>f</i>]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 EvaluationIgor A. Khalymbadzha0Ramil F. Fatykhov1Ilya I. Butorin2Ainur D. Sharapov3Anastasia P. Potapova4Nibin Joy Muthipeedika5Grigory V. Zyryanov6Vsevolod V. Melekhin7Maria D. Tokhtueva8Sergey L. Deev9Marina K. Kukhanova10Nataliya N. Mochulskaya11Mikhail V. Tsurkan12Department of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaEngelhardt Institute of Molecular Biology, 119991 Moscow, RussiaDepartment of Organic and Biomolecular Chemistry, Ural Federal University, 620002 Yekaterinburg, RussiaLeibniz Institute of Polymer Research Dresden, 01069 Dresden, GermanyWe have designed and synthesized a series of bioinspired pyrano[2,3-<i>f</i>]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2<i>H</i>,8<i>H</i>-pyrano[2,3-<i>f</i>]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction. Antiviral assay of the synthesized compounds showed that compound <b>4</b> has moderate activity against HIV-1 on enzymes and poor activity on the cell model. A molecular docking study demonstrates a good correlation between in silico and in vitro HIV-1 reverse transcriptase (RT) activity of the compounds when docked to the nonnucleoside RT inhibitor binding site, and alternative binding modes of the considered analogs of Calanolide A were established.https://www.mdpi.com/2313-7673/9/1/44Calanolide Aanti-HIV activityreverse transcriptasenon-nucleoside reverse transcriptase inhibitors (NNRTIs)Mannich reactionCH/CH-coupling |
| spellingShingle | Igor A. Khalymbadzha Ramil F. Fatykhov Ilya I. Butorin Ainur D. Sharapov Anastasia P. Potapova Nibin Joy Muthipeedika Grigory V. Zyryanov Vsevolod V. Melekhin Maria D. Tokhtueva Sergey L. Deev Marina K. Kukhanova Nataliya N. Mochulskaya Mikhail V. Tsurkan Bioinspired Pyrano[2,3-<i>f</i>]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation Biomimetics Calanolide A anti-HIV activity reverse transcriptase non-nucleoside reverse transcriptase inhibitors (NNRTIs) Mannich reaction CH/CH-coupling |
| title | Bioinspired Pyrano[2,3-<i>f</i>]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation |
| title_full | Bioinspired Pyrano[2,3-<i>f</i>]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation |
| title_fullStr | Bioinspired Pyrano[2,3-<i>f</i>]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation |
| title_full_unstemmed | Bioinspired Pyrano[2,3-<i>f</i>]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation |
| title_short | Bioinspired Pyrano[2,3-<i>f</i>]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation |
| title_sort | bioinspired pyrano 2 3 i f i chromen 8 ones ring c opened analogues of calanolide a synthesis and anti hiv 1 evaluation |
| topic | Calanolide A anti-HIV activity reverse transcriptase non-nucleoside reverse transcriptase inhibitors (NNRTIs) Mannich reaction CH/CH-coupling |
| url | https://www.mdpi.com/2313-7673/9/1/44 |
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