Monomyristin and Monopalmitin Derivatives: Synthesis and Evaluation as Potential Antibacterial and Antifungal Agents

In the present work, monoacylglycerol derivatives, i.e., 1-monomyristin, 2-monomyristin, and 2-monopalmitin were successfully prepared from commercially available myristic acid and palmitic acid. The 1-monomyristin compound was prepared through a transesterification reaction between ethyl myristate and 1,2-O-isopropylidene glycerol, which was obtained from the protection of glycerol with acetone, then followed by deprotection using Amberlyst-15. On the other hand, 2-monoacylglycerol derivatives were prepared through enzymatic hydrolysis of triglycerides in the presence of Thermomyces lanuginosa lipase enzymes. The synthesized products were analyzed using fourier transform infrared (FTIR) spectrophotometer, gas or liquid chromatography-mass spectrometer (GC-MS or LC-MS), and proton and carbon nuclear magnetic resonance (1H- and 13C-NMR) spectrometers. It was found that monomyristin showed high antibacterial and antifungal activities, while 2-monopalmitin did not show any activity at all. The 1-monomyristin compound showed higher antibacterial activity against Staphylococcus aureus and Aggregatibacter actinomycetemcomitans and also higher antifungal activity against Candida albicans compared to the positive control. Meanwhile, 2-monomyristin showed high antibacterial activity against Escherichia coli. The effect of the acyl position and carbon chains towards antibacterial and antifungal activities was discussed.

A competitive inhibitor of phospholipase A2 decreases surfactant phosphatidylcholine degradation by the rat lung

We have shown previously that radiolabelled phosphatidylcholine (PC) in liposomes or natural surfactant is removed from the alveolar space and metabolically recycled in a process that is stimulated by cyclic AMP (cAMP). In this study, we evaluated the effect of a transition-state phospholipid analogue (MJ33; 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol) that competitively inhibited acidic phospholipase A2 (PLA2) activity (pH 4.0) of lung homogenate by more than 97%, but had no effect on PLA2 activity at pH 8.5. MJ33 incorporated into unilamellar liposomes (dipalmitoyl PC/egg PC/cholesterol/phosphatidylglycerol, molar proportions 10:5:3:2) or co-sonicated with biosynthesized natural surfactant was instilled into the trachea of the anaesthetized rat; lungs were then removed for 2 h perfusion in the absence or presence of 0.1 mM-8-bromo cAMP. Total uptake for phospholipid was unchanged in the presence of the inhibitor MJ33. Degradation of labelled PC during 2 h perfusion in the absence of MJ33 was approx. 26% of that instilled for choline-labelled liposomal PC, 16% for liposomal PC labelled in the second fatty-acyl position, and 33% for choline-labelled natural surfactant. Degradation of PC was decreased by approx. 25-40% for each substrate in the presence of MJ33. Inhibition of lipid degradation depended on the mole fraction of MJ33 in the liposomes and was maximal at 1 mol%. These studies demonstrate a significant role for acidic Ca(2+)-independent PLA2 in the degradation of internalized alveolar PC, but further indicate that this enzyme accounts for a minor fraction of total lung PC metabolism.

Activity of phospholipase A2 in plasma increases in uremia

We measured phospholipase A2 (PLA2; EC 3.1.1.4) activity in normal and uremic plasma, using [1-14C]oleate-labeled autoclaved Escherichia coli as substrate. Hydrolysis of bacterial phospholipid by crude plasma from both groups was optimal at pH 5.5, was specific for the 2-acyl position of phospholipids, and had an absolute requirement for calcium. Activity was greatest in the presence of added Ca2+, 5 mmol/L, but this increase was inhibited by several divalent cations (Mg2+, Zn2+, Cu2+, Ba2+, Co2+, Pb2+, Fe2+) and by Fe3+. PLA2 activity was also inhibited by heparin at acid and alkaline pH, normal plasma being more sensitive than uremic plasma to this inhibition. Enzyme activity in undiluted plasma was eightfold greater in uremic than in normal plasma. Dilution of plasma by two to fourfold increased the total activity of both normal and uremic plasma. However, the relative differences in total activity between the groups remained constant (eight- to 11-fold). The cause and consequences of the increased PLA2 activity in uremia remain to be established.