Abstract:
Background and aims: Cancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs i.e. without an impact on normal cells. Sulfonamides are the classic group of chemotherapeutic drugs with a broad spectrum of pharmacological activity. Recent literature reports show that sulfonamide derivatives have antitumor activity in vitro and in vivo. Thus, the objective of this study was to synthesize novel pyrazolo[4,3-e]tetrazolo[1,5- b][1,2,4]triazine sulfonamide derivatives with anticancer potential against colon cancer cells. Results: The research carried out included MTT assay, DNA biosynthesis, cell cycle analysis, Annexin V binding assay, ethidium bromide/acridine orange staining, and caspase-8, -9, and -3/7 activity. Moreover, the concentrations of important molecules (sICAM-1, mTOR, Beclin-1, cathepsin B) involved in the pathogenesis and poor prognosis of colorectal cancer were also evaluated by ELISA. Obtained results demonstrated that the novel compounds were able to induce apoptosis through intrinsic and extrinsic pathways and was capable of decreasing sICAM1, mTOR, cathepsin B concentrations, whereas increased Beclin-1 concentration was detected in both colon cancer cell lines (DLD-1 and HT-29). Conclusions: The novel compounds represents promising multi-targeted potential in colorectal cancer, but further in vivo examinations are needed to confirm the claim. The most active derivative turned out to be tricyclic sulfonamide MM131 that possesses promising anticancer properties. It inhibits the viability and proliferation of DLD-1 and HT-29 cells. The molecular mechanism of action is associated with the induction of both extrinsic and intrinsic apoptotic pathways. This is related to increased caspase-8 and caspase-9 activity. MM131 leads to the inhibition of important proteins engaged in the progression and metastasis of colorectal cancer such as sICAM-1, cathepsin B, and mTOR.
Page(s):
47-47
DOI:
DOI not available
Published:
Journal: Abstract Book on Global Science Technology and Management Conference, Volume: 0, Issue: 0, Year: 2023
Keywords:
Cancer therapy
,
4triazine sulfonamide derivatives
,
novel pyrazolo4
,
3etetrazolo1
,
5b1