文獻中報導，親電子性基團可能可以增強四環黴素的抑作制用。而氟是親脂性原子，它具有一些特色，例如: (1)很強的電負度，使之可以穩定化合物上容易被降解的地方並避免產生代謝產物。因為某些代謝物可能具有細胞毒性，並可能會使藥物無效。另一個特徵是氟的大小與氫相似，因此我們的化合物在大小上不會被改變很多。由於氟化藥物具有很多優勢，因此在本研究中，我們嘗試使用F-TEDA-BF4在四環黴素衍生物4-demethylaminodoxycycline（CMT-8）上修飾上氟，然後利用HPLC，MS，NMR進行分析鑑定，接著使用HPLC純化，並利用明膠酶譜分析法(gelatin zymography)來分析此四環黴素衍生物抑制基質金屬蛋白酶的效果，最後採用MTT檢測此強力黴素衍生物的細胞毒性。在這項研究中，我們成功地將CMT-8 C4氟化，但由於在合成的機制上，會有酮-烯醇互變異構，使它存在表異構物。但好消息是它的細胞毒性很低，所以我們目前不考慮表異構物的問題。而在抑制基質金屬蛋白酶-9上，此化合物的效果不是很好，其最大抑制濃度的一半約為80 µg / ml，而先前本實驗室合成之CMT-8約為2.5µg / ml，DOX約為10µg / ml，因此CMT- 8仍然是這些藥物中抑制MMP-9表達最好的藥物。

Literature have reported that the lipophilicity a electron-donating group may enhance the inhibitory effect of tetracycline. Fluorine is a lipophilicity atom and it has some characteristic, such as it’s strong electronegativity which can stabilize the chemical not to be degraded into metabolite. Some metabolite may be cytotoxicity, and it may cause the medicine ineffective. The other characteristic is the size of fluorine is similar with hydrogen, so our compound may not change a lots of it’s size. Due to a lots of advantage of fluorine pharmaceutical, in this studies, we try to modify the doxycycline analog 4-dedimethylaminodoxycycline (CMT-8) by incorporating fluorine into it , using F-TEDA-BF4 of the fluorine sourse, and analysis the effect of this fluorinate inhibiting the matrix metalloproteinase by gelatin zymography, finally use MTT assay to test the cytotoxicity of doxycycline fluorinated analogs. In this study, we successfully synthesied CMT-8 fluorinated analogs on CMT-8 C4, which show an enantiomers. Although the existence of an enantiomers, it’s shows low cytotoxicity. However, the effect of inhibiting matrix metalloproteinase-9 is not very effective, it’s half maximal inhibitory concentration is about 80 µg/ml, 4-dedimethylaminodoxycycline (CMT-8) is about 2.5µg/ml and DOX is about 10µg/ml, so CMT-8 is still the most significant inhibitor of MMP-9 expression in these drugs.

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