Intermolecular complexation of low-molecular-weight succinoglycans directs solubility enhancement of pindolol.
The low-molecular-weight succinoglycans isolated from Sinorhizobium meliloti are repeating octasaccharide units consisting of monomers, dimers, and trimers. Pindolol is a beta-blocker used to treat cardiovascular disorders. We investigated the formation of complexes between pindolol and low-molecular-weight succinoglycan monomers (SGs). Even though SGs have a linear structure, the solubility of pindolol in the presence of SGs was increased up to 7-fold compared with methyl-β-cyclodextrin reported as the best solubilizer of pindolol. Complexation of SGs with pindolol was confirmed by nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Formation constants of complexes were determined from phase solubility diagrams. Conformation of complex was suggested based on a molecular docking study. The present study indicated that formation of pindolol/SGs complexes not only resulted in increased pindolol solubility but also could be useful for improving its clinical application as it did not affect cell viability.
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Institute for Ubiquitous Information Technology and Application (CBRU), Konkuk University, Seoul 143-701, South Korea.
Kyoungtea
K
Kim
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Institute for Ubiquitous Information Technology and Application (CBRU), Konkuk University, Seoul 143-701, South Korea.
Eunae
E
Cho
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Institute for Ubiquitous Information Technology and Application (CBRU), Konkuk University, Seoul 143-701, South Korea.
Jae Min
JM
Choi
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Institute for Ubiquitous Information Technology and Application (CBRU), Konkuk University, Seoul 143-701, South Korea.
Hwanhee
H
Kim
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Institute for Ubiquitous Information Technology and Application (CBRU), Konkuk University, Seoul 143-701, South Korea.
Ahri
A
Jang
BioChip Research Center, Hoseo University, Asan 336-795, South Korea.
Youngjin
Y
Choi
Department of Biological Science & Center for Biotechnology Research in UBITA, Konkuk University, Seoul 143-701, South Korea.
Im Soon
IS
Lee
Department of Bacteriology and Genetics, University of Wisconsin, Madison, WI, USA; Department of Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, WI, USA.
Jae-Hyuk
JH
Yu
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Institute for Ubiquitous Information Technology and Application (CBRU), Konkuk University, Seoul 143-701, South Korea. Electronic address: shjung@konkuk.ac.kr.
Seunho
S
Jung
D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D008970:Molecular Weight; D010869:Pindolol / Q000737:chemistry* / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000494:pharmacology; D016962:Sinorhizobium meliloti / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
D011135:Polysaccharides, Bacterial; D012702:Serotonin Antagonists; C056779:succinoglycan; D010869:Pindolol
Complexation; Cyclodextrin; Low-molecular-weight succinoglycans; Pindolol; Sinorhizobium meliloti; Solubility enhancement