A Method to Find the Effective Substance and FIC

A Method to Find the Effective Substance and FIC

 

The paper I read:

A Clerodane Diterpene from Callicarpa americana(미국 작살나무) Resensitizes Methicillin-Pesistant Staphylococcus aureus to β-Lactam Antibiotics

 

 

 

The point of this paper is the extract of C. americana has synergistic effect when it’s used with antibiotics; oxacillin against S. aureus. The effective substance is clerodane diterpenes, 16α-hydroxycelroda-3,13(14)-Z-dien-15,16-olide.

 

 

When oxacillin is used together, PBP-2a structure and its function get affected, however, when oxacillin is simply used alone, PBPs get affected but PBP-2a remained still. So this means that 16α-hydroxycelroda-3,13(14)-Z-dien-15,16-olide increase the sensitivity of S. aureus to oxacillin. Also 16α-hydroxycelroda-3,13(14)-Z-dien-15,16-olide showed synergy with fluoroquinolone antibiotics against MRSA by downregulating genes vital to expression of multidrug resistant efflux pumps like norA, norB, norC, mdeA and mepA.

If this kind of method is used, usage of vamcomycin which has nephrotoxicity will get reduced. It means that this method could lower the risk for treating MRSA.

 

<Things I learned from the paper>

How to find the effective substance.

A. Extract the crude drug with several different solvents and do some experiments to find which extract has the effect that I am looking for(e.g. acetate, acetone, methanol etc.).

B. After you find the extract with the effect that you are looking for, then you should go through another extraction just like process A. However, the point of this process is; using solutions with different proportions controlled precisely(e.g. solvent a: solvent b= 1:4).

C. After separation via chromatography, take some experiments with the sections that has been formed at the column. If you find the section with the outcome that you were looking for, take process B with that section.

D. Keep repeat the process B and C and if you think that there is only one material in the solution, take NMR to deduce it’s chemical structure.

 

2. When you use 2 different drugs

If you want you use 2 different drugs together, you should consider FICI(fractional inhibitory concentration). This index indicates rather they are at synergistic relation, antagonist relation or they could be at no relation. For example, when you are using 2 different drugs A and B, FIC A = (the amount of A when it is used with B)/(the amount of A when it is used alone). Usually, FIC value lower than 0.5 represents that they are in synergistic relation, between 0.5 to 4.0 represents that they are in no relation and higher than 4.0 represents that they are in antagonist relation.

So, if you want to use 2 different drugs combined together, you should consider FIC value to increase or decrease the effect of the drug.

 

 

 

 

 

 

Something that I felt doing this kind of study is just simply abstracting the paper is kind of less efficient work. So I decided to get ideas from the papers and design my own experiments that I am going to conduct when I return to school.