Broad Street Scientific Journal 2020

Table 4. StarDrop data table of CMTs, tetracycline, doxycycline, and minocycline through the analysis of an
Oral CNS Scoring Profile. The color scale ranges from green to red, with darker greens being indicators of
more effective drugs, and darker reds being indicators of less effective drugs.
Oral
CNS
Scoring
Profile
Compound logP logS 2C9
pKi
hERG
pIC50
BBB
log([brain])
:([blood])
BBB
category
HIA
category
P-gp
category
2D6
affinity
category
PPB90
category
0.03053 tetracycline -0.8803 3.002 4.742 2.599 -1.577 - - yes low low
0.08814 doxycycline -0.2456 2.833 4.739 2.659 -1.3 - + yes low low
0.1369 minocycline 0.4239 2.591 4.8 3.168 -1.221 - + yes low low
0.02148 CMT-1 -0.3233 1.843 4.91 2.232 -1.217 - - yes low low
0.03198 CMT-3 0.765 1.369 4.833 2.665 -1.094 - - yes lo low
0.06815 CMT-4 0.9379 1.837 5.02 2.371 -1.198 - + yes low low
0.03579 CMT-5 -0.3333 2.412 5.232 2.096 -1.552 - - yes low low
0.01162 CMT-6 -0.9992 2.177 4.971 2.035 -1.3 - - yes low low
0.03813 CMT-7 0.4774 1.556 4.886 2.429 -0.9871 - - yes low low
0.07435 CMT-8 0.1577 1.73 4.88 2.422 -1.206 - + yes low low
amino tetracycline and 12-deoxy-dedimethylamino tetracycline
respectively. CMT-3 is commercially available as
incyclinide while CMT-7 is not, so CMT-3 was the only
CMT taken into consideration in experimental data. In future
work, if other CMTs are available, they should also
be used to measure effectiveness as AD drugs, especially
CMT-7.
Figure 4. Paralysis assay of C. elegans paralysis 24
hours after temperature shift to 24 o C.
It has been shown that tetracycline and doxycycline are
effective at reducing paralysis in C. elegans [10]. Results
shown here support this while suggesting that CMT-3 is
also effective at reducing paralysis, potentially even better
than the two tetracycline analogs.
However, though data suggest that CMT-3 is overall
more effective than tetracycline and doxycycline, the data
show large drops and fluctuations during the time period
measured, probably due to a smaller sample size in each
trial performed. Additionally, there is a 10-hour long time
period lost in data collection that distorts the pattern of
paralysis as time goes on. In future work, the experimental
section should be replicated with a larger sample size and
ideally consistent 2-hour intervals throughout the entire
approximately 24-hour period, working to confirm the results
shown here.
4. Conclusion
It has been concluded through computational analysis
that CMTs can be predicted to interact with Aβ in a similar
manner to tetracycline and its natural analogs. Especially
successful CMTs include CMT-3 and 7, and in vivo
trials with model organism C. elegans, specifically temperature-dependent
strain CL2006, can model paralysis correlated
to Aβ expression. Experimental data shows that
CMT-3 does partially recover paralysis in this strain and
suggests that other CMTs may do the same.
Tetracycline and its analogs can be used for multiple
medicinal applications and can interact with Aβ aggregation
in transgenic models of C. elegans to protect them
from the paralysis phenotype. Certain CMTs have been
computationally modeled to behave in the same manner
to a similar and possibly better degree. This is especially
applicable to CMT-3 (6-deoxy-6-demethyl-4-dedimethylamino
tetracycline) and CMT-7 (12-deoxy-4-dedimethylamino
tetracycline) which have been suggested to be
better at preventing aggregation with the preformed Aβ
fibril and exhibit better interactions as oral drugs. Paralysis
assays performed with a transgenic model of C. elegans in
an in vivo study seem to exhibit a pattern indicating CMT-
3’s ability to prevent paralysis caused by Aβ aggregation
and may outperform both tetracycline and doxycycline in
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