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Harnessing the anti-cancer potential of linamarin: A computational study on design and hydrolysis mechanisms of its derivatives.
Liyanage, Senal D; Gunasekera, Dinara; Ratnaweera, Chinthaka N.
Afiliación
  • Liyanage SD; Department of Chemistry, Mississippi State University, Mississippi State, MS, 39762, USA.
  • Gunasekera D; New Frontier Bio, Inc., 48 Dunham Ridge, Suite 5600, Beverly, MA, 01915, USA.
  • Ratnaweera CN; Department of Chemistry, University of Ruhuna, Matara, Sri Lanka. Electronic address: nadun@chem.ruh.ac.lk.
J Mol Graph Model ; 128: 108716, 2024 05.
Article en En | MEDLINE | ID: mdl-38277856
ABSTRACT
Cassava extracts containing cyanogenic compounds demonstrate anticancer properties. The cyanogenic glucoside linamarin found abundantly in cassava can release hydrogen cyanide (HCN) upon hydrolysis, a potent cytotoxin. However, linamarin's hydrolysis mechanism by human enzymes is poorly delineated and constitutes a bottleneck for therapeutic development. This study aimed to investigate linamarin's hydrolysis mechanism by human ß-glucosidase and identify structural derivatives with enhanced hydrolytic potential using density functional theory calculations. Results revealed α-anomeric derivatives as promising, with leaving group ability and steric bulk strongly governing hydrolysability. We identified several linamarin analogs with predicted rapid hydrolysis kinetics that may enable swift cytotoxic HCN release against cancer cells. This investigation enriches understanding of cyanogenic glycoside reactivity to facilitate their development as targeted antineoplastic agents. The identified derivatives set the groundwork for experimental evaluation of enhanced linamarin-inspired compounds as innovative cancer therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Manihot / Neoplasias Límite: Humans Idioma: En Revista: J Mol Graph Model Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Manihot / Neoplasias Límite: Humans Idioma: En Revista: J Mol Graph Model Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
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