I have tested a plant extract for cytotoxic activity against cell lines and it showed potent activity?
The pure major isolated compounds have high values for IC50% and its amount is very small to be tested in-vivo.
The docking provides that these compounds have anti-neoplastic activities.
How do i explain that?
When the plant extract was fractionated, was each fraction tested for biological activity so that the active component(s) could be isolated? The active components are not necessarily the abundant ones. Also, the active components could be unstable, and degraded during purification and storage.
By the way, docking cannot be used to "prove" antineoplastic activity. Experimentation is required.
It depends on if your compound can specifically target cancer cell or not.
Most anti tumor compound has side effect because they are cytotoxic and may kill normal cell such as WBC.
Actually, I dont quite understand your question.
The term "Cytotoxicity" means the quality of being toxic to cells. Anti-tumor compound can kill tumor cell that means they are somehow being toxic to cell. How can an anti-tumor compound being not cytotoxic?
Very ambiguous question. Every chemotherapeutic agent is more or less cytotoxic to every cell in the body. Due to the clonal nature of malignant cell population in vivo, probability that a chemical is equally effective against all tumor cell clones is very remote unless you discovered a miracle adrug.
Dear, Vidyasagar Sriramoju
According to the criteria of the American National Cancer Institute, the cytotoxicity LC50 limit to consider a crude extract promising for further purification is lower than 30 μg/mL. and the cytotoxicity of pure compounds (LC50 < 4 μg/mL). for MTT assay
I already have LC50< 14 μg/mL for the crude extract. and i have been analyzed the extract and identified its major component. besides i have been isolated the major compounds by chromatographic separation and identified them by spectroscopic identification.
The cytotoxicity of pure compounds give LC50 more than 100 μg/mL which mean that it is not active according to NCI.
I have been tried to do Molecular docking by some biological docking simulation programs which gives me antineoplastic, chemopreventive, apoptosis agonist with probabiltiy more than 0.890 in many compounds of them.
my question have too aspects
firstly, could be there an explanation other than synergism explain how is the crude extracts potent cytotoxic while the pure major compounds not.
Is there another mechanisms than cytotoxicity for compounds that have anti-tumor activity to explain the results of docking.
N.B. the amounts of pure compounds is too small to do in vivo studies.
I hope it is clear now
It is possible and actually observed many times that the activity you observed for the crude extract is because of the minor components of the extract rather than the major components.
If you are claiming synergism to be the reason, I think you can easily verify this experimentally using the purified major components you isolated.
The docking results would be questionable, what was the target you did use for docking? Is this target over-expressed in the cells you did use for cytotoxicity assay? Based on your knowledge of the structure of the compounds and the potential target, can your compound actually reach this target in the cellular assay ?
Dear Mohammed Ezzat, I completely agree with Dr. Moustafa. It is not necessary that the major compound is giving the activity. It could be from any minor compound. I am also doing similar work. Sometimes synergism between compounds in that extract may give the activity. The best option is bio-assay guided fractionation. From the fraction you can test and finally purification can be done. Thanks.
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