Enhancing the water solubility of MyoNovin - a novel skeletal muscle regenerator

Abstract

Satellite precursor cells are normally quiescent but once activated they support skeletal muscle growth and regeneration by proliferating and differentiating into myoblasts. When an animal suffers from a muscle injury, quiescent satellite precursor cells are activated by nitric oxide (NO). MyoNovin (1-(3,4-Bis-nitrooxy-butoxy)-2-methoxy-benzene), as a NO donor, was developed to provide nitric oxide directly to the skeletal muscle and has been shown to promote satellite cell activation. A potential drawback of the current MyoNovin molecule is its poor water solubility. The aim of this work was to enhance the water-solubility of MyoNovin in order to improve its ease of formulation and possibly enhance its biological activity. The structure of MyoNovin (MN1) was modified with three different functional groups - methanesulfonyl (MN2), benzoic acid (MN3) and acetamide (MN4). The three novel MyoNovin analogs were identified and shown to have similar biological activity as with MyoNovin. All three MyoNovin analogs were found to have better water solubility.#Based on these results, two of the MyoNovin analogs (MN2 and MN3) had much better biological activity with respect to satellite activation and much improved water solubility and may be the most promising candidates for future studies.