Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors

Naoki Toyooka; Soushi Kobayashi; Dejun Zhou; Hiroshi Tsuneki; Tsutomu Wada; Hideki Sakai; Hideo Nemoto; Toshiyasu Sasaoka; H. Martin Garraffo; Thomas F. Spande; John W. Daly

doi:10.1016/j.bmcl.2007.08.045

Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors

Naoki Toyooka^*, Soushi Kobayashi, Dejun Zhou, Hiroshi Tsuneki, Tsutomu Wada, Hideki Sakai, Hideo Nemoto, Toshiyasu Sasaoka, H. Martin Garraffo, Thomas F. Spande, John W. Daly

^*Corresponding author for this work

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

30 Scopus citations

Abstract

We previously reported that the synthetic quinolizidine 1-epi-207I is a relatively selective blocker of α7 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked α7 and α4β2 currents with similar potencies. Alkaloids 235U and 251AA also showed similar potencies for blockade of α7 and α4β2 currents. Thus, based on these studies, it would appear that C4 substituents greater in length than the allyl of 1-epi-207I reduce α7-potency without affecting α4β2-potency.

Original language	English
Pages (from-to)	5872-5875
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2007.08.045
State	Published - 2007/11/01

Keywords

1-epi-207I
233A
235U
251AA
Neuronal nicotinic acetylcholine receptors
Poison-frog alkaloids

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2007.08.045

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Toyooka, N., Kobayashi, S., Zhou, D., Tsuneki, H., Wada, T., Sakai, H., Nemoto, H., Sasaoka, T., Garraffo, H. M., Spande, T. F., & Daly, J. W. (2007). Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors. Bioorganic and Medicinal Chemistry Letters, 17(21), 5872-5875. https://doi.org/10.1016/j.bmcl.2007.08.045

@article{7288357596d04eb4b33f0f06cfb4fc2b,

title = "Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors",

abstract = "We previously reported that the synthetic quinolizidine 1-epi-207I is a relatively selective blocker of α7 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked α7 and α4β2 currents with similar potencies. Alkaloids 235U and 251AA also showed similar potencies for blockade of α7 and α4β2 currents. Thus, based on these studies, it would appear that C4 substituents greater in length than the allyl of 1-epi-207I reduce α7-potency without affecting α4β2-potency.",

keywords = "1-epi-207I, 233A, 235U, 251AA, Neuronal nicotinic acetylcholine receptors, Poison-frog alkaloids",

author = "Naoki Toyooka and Soushi Kobayashi and Dejun Zhou and Hiroshi Tsuneki and Tsutomu Wada and Hideki Sakai and Hideo Nemoto and Toshiyasu Sasaoka and Garraffo, {H. Martin} and Spande, {Thomas F.} and Daly, {John W.}",

note = "Funding Information: We are grateful to Dr. Jerry A. Stitzel (University of Colorado) for providing us with plasmid DNA. We also thank Dr. John A. Dani (Baylor College of Medicine, Houston, TX) for support on electrophysiological data acquisition. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to N.T. and H.T.). Work at NIH was supported by intramural funds of NIDDK.",

year = "2007",

month = nov,

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doi = "10.1016/j.bmcl.2007.08.045",

language = "英語",

volume = "17",

pages = "5872--5875",

journal = "Bioorganic and Medicinal Chemistry Letters",

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Toyooka, N, Kobayashi, S, Zhou, D, Tsuneki, H , Wada, T , Sakai, H, Nemoto, H, Sasaoka, T, Garraffo, HM, Spande, TF & Daly, JW 2007, 'Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 21, pp. 5872-5875. https://doi.org/10.1016/j.bmcl.2007.08.045

TY - JOUR

T1 - Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors

AU - Toyooka, Naoki

AU - Kobayashi, Soushi

AU - Zhou, Dejun

AU - Tsuneki, Hiroshi

AU - Wada, Tsutomu

AU - Sakai, Hideki

AU - Nemoto, Hideo

AU - Sasaoka, Toshiyasu

AU - Garraffo, H. Martin

AU - Spande, Thomas F.

AU - Daly, John W.

N1 - Funding Information: We are grateful to Dr. Jerry A. Stitzel (University of Colorado) for providing us with plasmid DNA. We also thank Dr. John A. Dani (Baylor College of Medicine, Houston, TX) for support on electrophysiological data acquisition. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to N.T. and H.T.). Work at NIH was supported by intramural funds of NIDDK.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - We previously reported that the synthetic quinolizidine 1-epi-207I is a relatively selective blocker of α7 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked α7 and α4β2 currents with similar potencies. Alkaloids 235U and 251AA also showed similar potencies for blockade of α7 and α4β2 currents. Thus, based on these studies, it would appear that C4 substituents greater in length than the allyl of 1-epi-207I reduce α7-potency without affecting α4β2-potency.

AB - We previously reported that the synthetic quinolizidine 1-epi-207I is a relatively selective blocker of α7 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked α7 and α4β2 currents with similar potencies. Alkaloids 235U and 251AA also showed similar potencies for blockade of α7 and α4β2 currents. Thus, based on these studies, it would appear that C4 substituents greater in length than the allyl of 1-epi-207I reduce α7-potency without affecting α4β2-potency.

KW - 1-epi-207I

KW - 233A

KW - 235U

KW - 251AA

KW - Neuronal nicotinic acetylcholine receptors

KW - Poison-frog alkaloids

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U2 - 10.1016/j.bmcl.2007.08.045

DO - 10.1016/j.bmcl.2007.08.045

M3 - 学術論文

C2 - 17827002

AN - SCOPUS:34548859532

SN - 0960-894X

VL - 17

SP - 5872

EP - 5875

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors

Abstract

Keywords

ASJC Scopus subject areas

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