Aspects for development of novel antibacterial medicines using a vitamin D3 decomposition product in Helicobacter pylori infection.

Abstract

A previous study by our group demonstrated that a vitamin D3 decomposition product (VDP1) acts as the selective bactericidal substance on Helicobacter pylori. VDP1 is an indene compound modified with a carbonyl and an alkyl. The alkyl of VDP1 turned out to be a mandatory structure to exert effective bactericidal action on H. pylori. Meanwhile, it still remains to be clarified as to how influence the alteration of the carbonyl in VDP1 has on the anti-H. pylori activity. In this study, we synthesized novel VDP1 derivatives that replaced the carbonyl of VDP1 by various functional groups and investigated the antibacterial action of the VDP1 derivatives on H. pylori. VDP1 derivatives retaining either a hydroxy (VD3-1) or an acetic ester (VD3-3) exhibited more effective bactericidal action to H. pylori than VDP1. The replacement of the carbonyl of VDP1 by either an allyl acetate (VD3-2) or an acrylic acid (VD3-5) provided almost no change to the anti-H. pylori activity. Apart from this, an isomer of VDP1 (VD3-4) slightly improved anti-H. pylori activity of VDP1. Meanwhile, the replacement of the carbonyl of VDP1 by a methyl acrylate (VD3-6) attenuated the anti-H. pylori activity. As with VDP1, its derivatives also were suggested to exert the anti-H. pylori action through the interaction with myristic acid side chains of dimyristoyl-phosphatidylethanolamine, a characteristic membrane lipid constituent of this pathogen. These results indicate that it is capable of developing specific antibacterial medicines for H. pylori targeting the biomembranal dimyristoyl-phosphatidylethanolamine using VDP1 as the fundamental structure.