Design and synthesis of purine connected piperazine derivatives as novel inhibitors of Mycobacterium tuberculosis
Copyright © 2020 Elsevier Ltd. All rights reserved..
A series of novel purine linked piperazine derivatives were synthesized to identify new, potent inhibitors of Mycobacterium tuberculosis. The compounds were designed to target MurB disrupting the biosynthesis of the peptidoglycan and exert antiproliferative effects. The first series of purine-2,6-dione linked piperazine derivatives were synthesized using an advanced intermediate 1-(3,4-difluorobenzyl)-7-(but-2-ynyl)-3-methyl-8-(piperazin-1-yl)-1H-purine-2,6(3H,7H)-dione hydrochloride (6) which was coupled with varied carboxylic acid chloride derivatives. Following this piperazine linked derivatives were also synthesized from 6 using diverse isocyanate partners. The anti-mycobacterial activity of the analogues was tested againstMycobacterium tuberculosis H37Rv which revealed a cluster of six analogues (11, 24,27, 32, 33 and34), possessed promising activity. In comparison, a set of these new compounds possessed greater potencies relative to current drugs used in the clinic such as Ethambutol. These results were also correlated with computational molecular docking analysis, providing models for strong interactions of the inhibitors with MurB providing a template for the future development of preclinical agents against Mycobacterium tuberculosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Bioorganic & medicinal chemistry letters - 30(2020), 22 vom: 15. Nov., Seite 127512 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Konduri, Srihari [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.06.2021 Date Revised 22.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmcl.2020.127512 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM314442693 |
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| 520 | |a Copyright © 2020 Elsevier Ltd. All rights reserved. | ||
| 520 | |a A series of novel purine linked piperazine derivatives were synthesized to identify new, potent inhibitors of Mycobacterium tuberculosis. The compounds were designed to target MurB disrupting the biosynthesis of the peptidoglycan and exert antiproliferative effects. The first series of purine-2,6-dione linked piperazine derivatives were synthesized using an advanced intermediate 1-(3,4-difluorobenzyl)-7-(but-2-ynyl)-3-methyl-8-(piperazin-1-yl)-1H-purine-2,6(3H,7H)-dione hydrochloride (6) which was coupled with varied carboxylic acid chloride derivatives. Following this piperazine linked derivatives were also synthesized from 6 using diverse isocyanate partners. The anti-mycobacterial activity of the analogues was tested againstMycobacterium tuberculosis H37Rv which revealed a cluster of six analogues (11, 24,27, 32, 33 and34), possessed promising activity. In comparison, a set of these new compounds possessed greater potencies relative to current drugs used in the clinic such as Ethambutol. These results were also correlated with computational molecular docking analysis, providing models for strong interactions of the inhibitors with MurB providing a template for the future development of preclinical agents against Mycobacterium tuberculosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Molecular docking studies | |
| 650 | 4 | |a Mycobacterium Tuberculosis | |
| 650 | 4 | |a Piperazines | |
| 650 | 4 | |a Purines | |
| 650 | 4 | |a Spectroscopic study | |
| 650 | 4 | |a X-ray analysis | |
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| 650 | 7 | |a Piperazine |2 NLM | |
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| 700 | 1 | |a Krishna, Vagolu Siva |e verfasserin |4 aut | |
| 700 | 1 | |a Sriram, Dharmarajan |e verfasserin |4 aut | |
| 700 | 1 | |a Behera, J N |e verfasserin |4 aut | |
| 700 | 1 | |a Siegel, Dionicio |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Koya Prabhakara |e verfasserin |4 aut | |
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