Interaction of a Biguanide Compound with Membrane Model Interface Systems: Probing the Properties of Antimalaria and Antidiabetic Compounds

Abstract

Since membrane penetration is important for drug efficacy, how antimalarial precursor material 1-phenylbiguanide (PBG) interacts with an interface was characterized using a reverse micelle (RM) model system. (1)H NMR studies show that PBG partitions across the membrane interface. Specifically, the (1)H NMR studies showed that the 1-phenylbiguanide compound in an aqueous environment changed when placed near an interface. PBG is known to affect hydrogen bonding in water, and as the size of the RMs changes, the water organization in the water pool is changed. The NOESY spectrum of PBG in AOT RM contains cross-peak signals between the PBG protons and AOT protons, which is consistent with the penetration of the PBG into the interface. At the same time, there is a cross peak between the biguanide moiety and the HOD signal. This shows that these NH protons are near the HOD protons, placing the biguanide functional group in the water pool. Preliminary differential FTIR spectroscopic studies confirmed this location. In summary, we found that PBG interacts with different regions of the interface, with the phenyl group penetrating the hydrophobic interface while the biguanide remains in the water pool.

A Structural Basis for Biguanide Activity

“…The primary direct targets of metformin that have been identified are mitochondrial: complex I of the respiratory chain 9, 10 as well as more recently identified targets including hexokinase II 11 and glycerophosphate dehydrogenase 12 . Directly-targeted non-mitochondrial enzymes include AMP deaminase 13 , and other structures such as the cell membrane 14 have also been proposed. Increasing evidence identifies the gut microbiome, and more generally the gastrointestinal tract, as important mediators of biguanide effects 15–17 .…”

Structure Dependence of Pyridine and Benzene Derivatives on Interactions with Model Membranes

“…The NIC concentration was increased to obtain a greater signal to noise ratio in the 1 H NMR spectra of the RMs. Each aqueous stock solution was then pipetted into 2 mL aliquots and the pD (pD = pH + 0.4) 30–46 of each aliquot was adjusted using NaOD or DC1 solutions (5.0,1.0, and 0.1 M). The pD will be referred to as pH for the rest of this manuscript as is commonly done.…”

“…The pD will be referred to as pH for the rest of this manuscript as is commonly done. 30–46 The pD of the aliquots was adjusted to a range between 1.2 and 9.0 for later use in determination the pKa in D 2 O and in the w 0 16 RMs.…”

Physicochemical investigation of antibacterial Moxifloxacin interacting with quaternary ammonium disinfectants

“…gastric acid) [8]. Besides the solubilizing capacity, the hydrophilic corona of micelle is capable to create a highly water-bound barrier, which potentially blocks the adhesion of other hydrophobic compounds [9][10][11].…”