Abstract
The cytochrome bc1 complex (the bc1 complex or complex III) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1 complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out, and the results implied that several compounds demonstrated good activities against succinate-cytochrome reductase (SCR, a mixture of mitochondrial complex II and the bc1 complex). Further studies confirmed that 3e′ a representative compound in this paper, was identified as an inhibitor of the bc1 complex. Furthermore, computational simulations were also performed to better understand binding of 3e′ to the enzyme complex, which indicated that 3e′ should bind to the Qo site of the bc1 complex. Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1 complex inhibitors.
| Original language | English |
|---|---|
| Pages (from-to) | 1897-1900 |
| Number of pages | 4 |
| Journal | Chinese Chemical Letters |
| Volume | 29 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 1 Dec 2018 |
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Keywords
- Biochemical evaluation
- Computational simulation
- Cytochrome bc complex
- Inhibitor
- N-(4-Aryloxyphenyl)phthalimide
- Synthesis
ASJC Scopus subject areas
- Chemistry(all)
Cite this
Synthesis, biochemical evaluation and computational simulations of new cytochrome bc1 complex inhibitors based on N-(4-aryloxyphenyl) phthalimides. / Cheng, Hua; Fu, Yan; Chang, Qing; Zhang, Ni; Bu, Mengwei; Niu, Yan; Wu, Qiongyou; Chen, Cheng; Verpoort, Francis.
In: Chinese Chemical Letters, Vol. 29, No. 12, 01.12.2018, p. 1897-1900.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis, biochemical evaluation and computational simulations of new cytochrome bc1 complex inhibitors based on N-(4-aryloxyphenyl) phthalimides
AU - Cheng, Hua
AU - Fu, Yan
AU - Chang, Qing
AU - Zhang, Ni
AU - Bu, Mengwei
AU - Niu, Yan
AU - Wu, Qiongyou
AU - Chen, Cheng
AU - Verpoort, Francis
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The cytochrome bc1 complex (the bc1 complex or complex III) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1 complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out, and the results implied that several compounds demonstrated good activities against succinate-cytochrome reductase (SCR, a mixture of mitochondrial complex II and the bc1 complex). Further studies confirmed that 3e′ a representative compound in this paper, was identified as an inhibitor of the bc1 complex. Furthermore, computational simulations were also performed to better understand binding of 3e′ to the enzyme complex, which indicated that 3e′ should bind to the Qo site of the bc1 complex. Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1 complex inhibitors.
AB - The cytochrome bc1 complex (the bc1 complex or complex III) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1 complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out, and the results implied that several compounds demonstrated good activities against succinate-cytochrome reductase (SCR, a mixture of mitochondrial complex II and the bc1 complex). Further studies confirmed that 3e′ a representative compound in this paper, was identified as an inhibitor of the bc1 complex. Furthermore, computational simulations were also performed to better understand binding of 3e′ to the enzyme complex, which indicated that 3e′ should bind to the Qo site of the bc1 complex. Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1 complex inhibitors.
KW - Biochemical evaluation
KW - Computational simulation
KW - Cytochrome bc complex
KW - Inhibitor
KW - N-(4-Aryloxyphenyl)phthalimide
KW - Synthesis
UR - http://www.scopus.com/inward/record.url?scp=85057110534&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057110534&partnerID=8YFLogxK
U2 - 10.1016/j.cclet.2018.10.008
DO - 10.1016/j.cclet.2018.10.008
M3 - Article
AN - SCOPUS:85057110534
VL - 29
SP - 1897
EP - 1900
JO - Chinese Chemical Letters
JF - Chinese Chemical Letters
SN - 1001-8417
IS - 12
ER -