ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

A novel sulfonamide derivative as a strong and selective apototic agent against hematological malignancies

Álisson Bigolin, Mariana F. Maioral, Natália M. Stefanes, Alessandra Mascarello, Louise D. Chiaradia-Delatorre, Ricardo J. Nunes, Rosendo A. Yunes, and Maria Cláudia Santos-Silva

Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, Florianópolis, Brazil

E-mail: maria.claudia.silva@ufsc.br

Received: 12 July 2019  Accepted: 29 October 2019

Abstract:

Currently available chemotherapeutic drugs against hematological malignancies have several adverse effects and are associated with high mortality rates. Thus, in this study we evaluated the cytotoxic effect of 26 new sulfonamide derivatives on acute leukemia and multiple myeloma cells in order to try to discover a new selective and safe compound that might be used as a prototype for new chemotherapeutic agents. The most cytotoxic compound, DFS16, reduced the cell viability of K562, Jurkat and MM.1S cells in a concentration- and time- dependent manner and it was significantly less cytotoxic to non-tumor cells. On acute leukemia cells, sulfonamide DFS16 activated intrinsic and extrinsic apoptosis with Bax/Bcl-2 inversion, increased FasR expression and ΔΨm loss. In K562, DFS16 induced apoptosis by caspase-3 activation, while in Jurkat, it induced AIF release and caspase-3 independent apoptosis. In multiple myeloma, DFS16 induced cell cycle arrest at the G2/M phase and apoptosis with ΔΨm loss. Altogether, the results suggest that the new sulfonamide derivative DFS16 induces apoptotic-like cell death in acute leukemia and multiple myeloma cells. DFS16 is a promising new molecule that could be used as a prototype for the development of chemotherapeutics against hematological malignancies.

Keywords: Sulfonamide; Acute leukemia; Multiple myeloma; Cytotoxicity; Cell cycle; Apoptosis

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-019-00984-7

Chemical Papers 74 (9) 2965–2976 (2020)