Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer in vitro

Griselda A Cabral-Pacheco; Virginia Flores-Morales; Idalia Garza-Veloz; Miriam Damián-Sandoval; Rosa B Martínez-Flores; María C Martínez-Vázquez; Iván Delgado-Enciso; Iram P Rodriguez-Sanchez; Margarita L Martinez-Fierro

doi:10.3892/etm.2023.12335

Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer in vitro

Exp Ther Med. 2023 Dec 4;27(1):47. doi: 10.3892/etm.2023.12335. eCollection 2024 Jan.

Authors

Griselda A Cabral-Pacheco¹, Virginia Flores-Morales², Idalia Garza-Veloz¹, Miriam Damián-Sandoval¹, Rosa B Martínez-Flores¹, María C Martínez-Vázquez¹, Iván Delgado-Enciso^{3

4}, Iram P Rodriguez-Sanchez⁵, Margarita L Martinez-Fierro¹

Affiliations

¹ Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Autonomous University of Zacatecas, Zacatecas 98160, Mexico.
² Laboratory of Asymmetric Synthesis and Bio-Chemoinformatics, Chemical Engineering, Autonomous University of Zacatecas, Zacatecas 98160, Mexico.
³ School of Medicine, University of Colima, Colima 28040, Mexico.
⁴ Cancerology State Institute, Colima State Health Services, Colima 28085, Mexico.
⁵ Molecular and Structural Physiology Laboratory, School of Biological Sciences, Autonomous University of Nuevo Leon, Nuevo León 66455, Mexico.

Abstract

The present study highlighted the repositioning of the drug dapsone (DDS) for cancer therapy. Due to its mechanism of action, DDS has a dual effect as an antibiotic and as an anti-inflammatory/immunomodulator; however, at high doses, it has important adverse effects. The derivative DDS-13 [N,N'-(sulfonyl bis (4,1-phenylene)) dioctanamide] was synthesized through an N-acylation reaction to compare it with DDS. Its cytotoxic effects in cancer cells (DU145 and HeLa) and non-cancer cells (HDFa) were observed at concentrations ranging 0.01-100 µM and its physicochemical/pharmacokinetic properties were analyzed using the SwissADME tool. The objectives of the present study were to evaluate the anticancer activity of both DDS and DDS-13 and to identify the physicochemical and pharmacokinetic properties of DDS-13. The results showed that DDS-13 presented a cytotoxic effect in the DU145 cell line (IC₅₀=19.06 µM), while DDS showed a cytotoxic effect on both the DU145 (IC₅₀=11.11 µM) and HeLa (IC₅₀=13.07 µM) cell lines. DDS-13 appears to be a good cytotoxic candidate for the treatment of prostate cancer, while DDS appears to be a good candidate for both cervical and prostate cancer. Neither candidate showed a cytotoxic effect in non-cancerous cells. The different pharmacokinetic properties of DDS-13 make it a new candidate for evaluation in preclinical models for the treatment of cancer.

Keywords: cancer; cytotoxicity; dapsone; in vitro model; synthetic derivative.

Grants and funding

Funding: The present study was funded by the Academic Unit of Human Medicine and Health Sciences of the Autonomous University of Zacatecas and by CONACYT via a scholarship fund (grant no. 2021-000018-02NACF-15274).