Rediocides A and G as Potential Antitoxins Against Cobra Venom |
| |
Authors: | Maleeruk Utsintong Atchara Kaewnoi Wichet Leelamanit Arthur J. Olson Opa Vajragupta |
| |
Affiliation: | 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri‐Ayudhya Road, Bangkok 10400, Thailand, (phone:+662‐6448677 ext. 5402, 1410;2. fax: +662‐6448695);3. Department of Chemistry, Faculty of Science and Technology, Bansomdejchaopraya Rajabhat University, Bangkok 10600, Thailand;4. Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand;5. The Scripps Research Institute, Molecular Graphics Laboratory, Department of Molecular Biology, California 92037, USA |
| |
Abstract: | Rediocides A and G, the principle components of Trigonostemon reidioides (Kurz ) Craib , which is known as Lotthanong in Thai, were investigated for a detoxification mechanism against Naja kaouthia venom by in silico, in vitro, and in vivo methods. Molecular dockings of α‐cobratoxin with rediocides A and G were performed, and the binding energies were found to be ?14.17 and ?14.14 kcal/mol, respectively. Rediocides bind to α‐cobratoxin at the same location as α‐cobratoxin binds to the nicotinic acetylcholine receptor (nAChR), i.e., at the Asp27, Phe29, Arg33, Gly34, Lys35, and Val37 residues. α‐Cobratoxin cannot bind to nAChR, because some of its binding sites are occupied with rediocides. From in vitro SDS‐PAGE, it was found that rediocides can diminish the bands of α‐cobratoxin. In the presence of acetylcholine‐binding protein (AChBP), it was apparent that rediocides can bind both α‐cobratoxin and AChBP. From an in vivo test, it was found that injection of rediocides at 0.5 mg/kg immediately after an α‐cobratoxin dose of three times LD50 cannot prolong the survival time of mice. However, rediocide can prolong the survival time, if it is injected 30 min before the injection of α‐cobratoxin. The in vitro SDS‐PAGE and the in vivo results support the in silico detoxification mechanism of rediocides against cobra venom at a molecular level. |
| |
Keywords: | Rediocides A and G Trigonostemon reidioides Naja kaouthia α ‐Cobratoxin Antitoxins Antivenoms Detoxification |
|
|