Indene Compounds Synthetically Derived from Vitamin D Have Selective Antibacterial Action on Helicobacter pylori

• DOI: 10.1002/lipd.12043
• Publication Date: 2018-05-16T08:17:02Z
• Authors: Kiyofumi Wanibuchi; Kouichi Hosoda; Masato Ihara; Kentaro Tajiri; Yuki Sakai; Hisashi Masui; Takashi Takahashi; Yoshikazu Hirai; Hirofumi Shimomura
• Keywords: Lipidology; Indene

Helicobacter pylori infects the human stomach and is closely linked with development of gastric cancer. When detected, this pathogen can be eradicated from using wide-spectrum antibiotics. However, year by year, H. strains resistant to antibacterial action antibiotics have been increasing. The new substances effective against drug-resistant urgently required. Our group has recently identified extremely selective bactericidal effects in (1R,3aR,7aR)-1-[(1R)-1,5-dimethylhexyl]octahydro-7a-methyl-4H-inden-4-one (VDP1) (otherwise known as Grundmann's ketone), an indene compound derived decomposition vitamin D3 proposed mechanism whereby VDP1 induces bacteriolysis interacting at least PtdEtn (dimyristoyl-phosphatidylethanolamine [di-14:0 PtdEtn]) retaining two 14:0 fatty acids membrane lipid constituents. In study, we synthesized compounds ((1R,3aR,7aR)-1-((2R,E)-5,6-dimethylhept-3-en-2-yl)-7a-methyloctahydro-4H-inden-4-one [VD2-1], (1R,3aR,7aR)-1-((S)-1-hydroxypropan-2-yl)-7a-methyloctahydro-1H-inden-4-ol [VD2-2], (1R,3aR,7aR)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-ol [VD3-1]) either D2 or materials. VD2-1 VD3-1 selectively disrupted di-14:0 vesicles without destructing (dipalmitoyl-phosphatidylethanolamine) 16:0 acids. contrast, VD2-2, lacking alkyl group, had no influence on structural stability both vesicles. addition, exerted affecting viability commonplace bacteria. Meanwhile, VD2-2 almost forfeited pylori. These results suggest that a crucial conformation interact constituents ultimately induced.