Anti-Ovarian Cancer Conotoxins Identified from <i>Conus</i> Venom

Shuang Ju; Yu Zhang; Xijun Guo; Qinghui Yan; Siyi Liu; Bokai Ma; Mei Zhang; Jiaolin Bao; Sulan Luo; Ying Fu

doi:10.3390/molecules27196609

Molecules (Oct 2022)

Anti-Ovarian Cancer Conotoxins Identified from <i>Conus</i> Venom

Shuang Ju,
Yu Zhang,
Xijun Guo,
Qinghui Yan,
Siyi Liu,
Bokai Ma,
Mei Zhang,
Jiaolin Bao,
Sulan Luo,
Ying Fu

Affiliations

Shuang Ju: Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
Yu Zhang: Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
Xijun Guo: Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
Qinghui Yan: Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
Siyi Liu: Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
Bokai Ma: Beijing Key Laboratory of Organic Materials Testing Technology & Quality Evaluation, Institute of Analysis and Testing, Beijing Academy of Science and Technology, Beijing 100094, China
Mei Zhang: Beijing Key Laboratory of Organic Materials Testing Technology & Quality Evaluation, Institute of Analysis and Testing, Beijing Academy of Science and Technology, Beijing 100094, China
Jiaolin Bao: Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
Sulan Luo: Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
Ying Fu: Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China

DOI: https://doi.org/10.3390/molecules27196609
Journal volume & issue: Vol. 27, no. 19
p. 6609

Abstract

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Conotoxins constitute a treasury of drug resources and have attracted widespread attention. In order to explore biological candidates from the marine cone snail, we isolated and identified three novel conopeptides named as Vi14b, Vi002, Vi003, three conotoxin variants named as Mr3d.1, Mr3e.1, Tx3a.1, and three known conotoxins (Vi15a, Mr3.8 and TCP) from crude venoms of Conus virgo, Conus marmoreus and Conus texile. Mr3.8 (I-V, II-VI, III-IV) and Tx3a.1 (I-III, II-VI, IV-V) both showed a novel pattern of disulfide connectivity, different from that previously established for the µ- and ψ-conotoxins. Concerning the effect on voltage-gated sodium channels, Mr3e.1, Mr3.8, Tx3a.1, TCP inhibited Nav1.4 or Nav1.8 by 21.51~24.32% of currents at semi-activated state (TP2) at 10 μmol/L. Certain anti-ovarian cancer effects on ID-8 cells were exhibited by Tx3a.1, Mr3e.1 and Vi14b with IC50 values of 24.29 µM, 54.97 µM and 111.6 µM, respectively. This work highlights the role of conotoxin libraries in subsequent drug discovery for ovarian cancer treatment.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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