Background: The role of microtubules in cell division and signaling, intercellular transport,
and mitosis has been well known. Hence, they have been targeted for several anti-cancer drugs.
Methods: A series of 3-(alkylthio)-5,6-diphenyl-1,2,4-triazines were prepared and evaluated for
their cytotoxic activities in vitro against three human cancer cell lines; human colon carcinoma cells
HT-29, human breast adenocarcinoma cell line MCF-7, human Caucasian gastric adenocarcinoma
cell line AGS as well as fibroblast cell line NIH-3T3 by MTT assay. Docking simulation was performed
to insert these compounds into the crystal structure of tubulin at the colchicine binding site
to determine a probable binding model. Compound 5d as the most active compound was selected
for studying of microtubule disruption.
Results: Compound 5d showed potent cytotoxic activity against all cell lines. The molecular modeling
study revealed that some derivatives of triazine strongly bind to colchicine binding site. The
tubulin polymerization assay kit showed that the cytotoxic activity of 5d may be related to inhibition
of tubulin polymerization.
Conclusion: The cytotoxicity and molecular modeling study of the synthesized compounds with
their inhibition activity in tubulin polymerization demonstrate the potential of triazine derivatives
for development of new anti-cancer agents.