Synthesis, Molecular Docking
Study, and Cytotoxic Activity of 3,4-diaryl-5-(4-pyridinyl)-1,2,4-oxadiazole
Author(s):
Bita Zareian, Sajad Ghadbeighi, Amirali Amirhamzeh, Seyed N.
Ostad, Abbas Shafiee and Mohsen AminiPages 394-401 (8)
Abstract:
Background: Triaryl oxadiazoles have been proven to be useful agents against various types of cancer cell lines. Nevertheless, their mechanism of action is not fully understood.
Objective: Synthesis and cytotoxic activity of a new group of
triaryl oxadiazoles; 3,4-diaryl-5-(4- pyridinyl)-1,2,4-oxadiazole derivatives,
will be discussed in this study. Their cytotoxic activity has been examined in
4 different cell lines by MTT method.
Method: 3,4-Diaryl-5-(4-pyridinyl)-1,2,4-oxadiazole derivatives
were prepared from condensation of different imines with 4-substituted
benzohydroxyiminoyl chlorides. The antiproliferative activity of the final
compounds was examined in MCF-7, AGS, HT-29 and NIH3T3 cell lines by MTT assay,
using different concentrations of each compound to determine their IC50. The
cytotoxic activity of paclitaxel, doxorubicin and combretastatin A-4 was
evaluated as positive controls.
Results: All compounds demonstrated cytotoxic activity in
mentioned cell lines, in a dose dependent manner. Among all, 6d-2 showed the
highest cytotoxicity in AGS and MCF-7 cell lines with IC50 19.84 and 9.91
respectively and 6c-2 was the most potent in HT-29 with IC50 27.60. In
addition, 6c-1, one of the most potent compounds, showed an interestingly low
cytotoxic effect on NIH3T3 cell line, which is a noncancerous cell line. In the
molecular modeling study, all compounds had comparable binding energy in
Colchicine binding site and 6c-2 had the best-predicted binding energy.
Conclusion: Together, our data suggest that the synthesized
compounds have a partially selective mechanism of action against cancer cells
and possibly a lower toxic effect on normal cells, making them interesting
candidates for the synthesis of new anticancer agents.
Keywords:
1, 2, 4-Oxadiazole, anticancer, cytotoxicity, molecular docking,
tubulin.
Affiliation:
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran
University of Medical Sciences, Tehran, Iran.
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