Synthesis of novel analogues on the α-carbon of houttuyfonate and SAR analysis of antibacterial activity with MOPAC

Abstract

Three novel a-carbon derivatives of houttuyfonate-HOU-C 8 C 1 , HOU-C 8 C 2 , and HOU-C 8 C 4 -were designed and synthesized, and tested for their in vitro antibacterial activities against seven bacterial strains. A set of molecular properties of houttuyfonate and its five analogues were analyzed by MOPAC. Results indicated that the antibacterial activity of HOU-C 8 C 1 is lower than that of HOU-C 8 . However, among HOU-C 8 C n (n = 1, 2, 4), as the hydrophobicity increased so did the activity, especially against Gram-positive bacteria. For the isomeric compounds HOU-C 8 C 2 and HOU-C 10 , HOU-C 8 C 4 , and HOU-C 12 , the more negative the charges on carbon atom 2, the stronger the antibacterial activity exhibited. This suggests that the C(2) position is the antibacterial active center of houttuyfonate analogues, and that the weak antibacterial activities are possibly caused by the net negative charges on houttuyfonate homologues.

In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus

“…Although antibacterial mechanism of SNH remains unknown, it was indicated that SNH exerted its antimicrobial effect mainly through binding of non-polar tail group to bacterial hydrophobic membrane proteins or cytoplasmic enzymes [18,25,26]. The hydrophobic lipid bilayer of cell membrane might be another target of aliphatic chain of SNH, but it seems that a repulsive force between the negatively charged membrane and the anionic hydrophilic moiety of SNH may weaken the potential interaction [27]. This might be an explanation of higher susceptibility of gram positive bacteria to SNH than gram negative bacteria, which have higher negative charge on the outer membrane due to presence of abundant anion charged phospholipids and lipopolysaccharides [28].…”

One-Pot Conversion of Aldehyde Sodium Bisulfites into Nitriles

“…[11] The adducts are not only used extensively in diverse products such as vitamin K 3 [12] and houttuynium sodium bisulfate, [13] but also in purification of thermally unstable aldehydes such as phenylacetaldehyde because aldehyde groups can be easily liberated from the bisulfite adducts when treated with acidic or basic aqueous solution. The high efficacy and ease of purification procedures prompted us to investigate application of bisulfite adducts to synthesize nitriles.…”