In vitro Cytotoxic Study of Benzylthio-triazol-5-haloisatin Scaffolds and their Evaluation on Supernatants Activities and Levels of MMP-2 and MMP-9 in MCF-7 Cell Line

Angiogenesis is the formation of new blood capillaries, and it is important for physiological processes such as growth and development and pathological conditions such as tumor growth and metastasis. Angiogenesis inhibition is considered very useful in the prevention and treatment of cancer. Matrix metalloproteinases (MMPs) are a family approximately consists of 28 zinc-dependent content endopeptidase which degrade the extracellular matrix (ECM) and play an important role on angiogenesis development and tumor metastasis. Therefore, inhibition of MMPs prevents the angiogenesis. The expression and levels of MMP-2 and MMP-9 is increased in many human tumors, including ovarian, breast and prostate tumors. In this study, cytotoxic effects of (Z)-3-((5-(benzylthio)-4H-1,2,4-triazol-3-yl)imino)-5-haloindolin-2-one derivatives 1a-1l were evaluated in MCF-7 (human breast adenocarcinoma) cell line by MTT assay. Then, the potency of the tested of some synthesized compounds was evaluated on supernatants activities and levels of MMP-2 and MMP-9 by gelatin zymography and ELISA methods. Among the tested compounds, 1j, 1l and 1k had the greatest cytotoxicity against MCF-7 cell line compared to the positive (sunitinib) and negative (DMSO) controls. Moreover, our observations indicated that the compounds 1j, 1l and 1k decreased the supernatants activities of MMP-2 and MMP-9 more than others and all of the tested compounds considerably decreased the supernatants levels of MMP-9. Finally, our findings suggest that the tested derivatives are probably able to inhibit macromolecules like MMPs which have essential role in angiogenesis pathway.