Selecting Potential Neuronal Drug Leads from Conotoxins of Various Venomous Marine Cone Snails in Bali, Indonesia

Anak A R Sudewi; Ni M Susilawathi; Bayu K Mahardika; Agung N Mahendra; Made Pharmawati; Mark A Phuong; Gusti N Mahardika

doi:10.1021/acsomega.9b03122

Selecting Potential Neuronal Drug Leads from Conotoxins of Various Venomous Marine Cone Snails in Bali, Indonesia

ACS Omega. 2019 Nov 6;4(21):19483-19490. doi: 10.1021/acsomega.9b03122. eCollection 2019 Nov 19.

Authors

Anak A R Sudewi¹, Ni M Susilawathi¹, Bayu K Mahardika², Agung N Mahendra¹, Made Pharmawati³, Mark A Phuong⁴, Gusti N Mahardika^{2

5}

Affiliations

¹ Neurology Department of the Faculty of Medicine and Pharmacology Department of the Faculty of Medicine, Udayana University, Jl. Sudirman, Denpasar 80226, Bali, Indonesia.
² The Animal Biomedical and Molecular Biology Laboratory, Udayana University of Bali, Jl. Sesetan-Markisa 6, Denpasar 80223, Bali, Indonesia.
³ Faculty of Mathematic and Natural Sciences, Udayana University of Bali, Kampus Bukit Jimbaran, Badung 80361, Bali, Indonesia.
⁴ Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles 90095, California, United States.
⁵ The Indonesian Biodiversity Research Center, Jl. Sudirman, Denpasar 80225, Bali, Indonesia.

Abstract

Many conotoxins, natural peptides of marine cone snails, have been identified to target neurons. Here, we provide data on pharmacological families of the conotoxins of 11 species of cone snails collected in Bali. The identified definitive pharmacological families possibly targeting neuronal tissues were α (alpha), ι (iota), κ (kappa), and ρ (rho). These classes shall target nicotinic acetylcholine receptors, voltage-gated Na channels, voltage-gated K channels, and α1-adrenoceptors, respectively. The VI/VII-O3 conotoxins might be prospected as an inhibitor of N-methyl-d-aspartate. Con-ikot-ikot could be applied as an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blocker medicine. The definitive pharmacology classes of conotoxins as well as those yet to be elucidated need to be further established and verified.