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<p>Prostate cancer is among the most common in the world. Since it is a very resistant type of cancer, the search for new therapeutic alternatives becomes crucial. Aiming to research new molecules to treat prostate cancer, a set of five derivatives of the previously proven antiprostatic LQB-118 molecules were synthesized, and their in vitro antitumor action was screened by MTT and Trypan Blue dye exclusion assays. The cell cycle and cell death by apoptosis were analyzed using flow cytometry. The derivatives LQB-471, LQB-472, LQB-473, LQB-474, and LQB-475 cytotoxicities were analyzed in hormone-sensitive (LNCaP) and resistant (PC3) prostate tumor cell lines, as well as in the Vero non-tumor cell line. LQB-471, LQB-472, and LQB-474 induced cytotoxicity in both tumor cell lines, with LQB-472 being the most active, acting in a time and concentration-dependent manner in both prostate tumor lineages. In 72&#xa0;h of incubation, LQB-472 showed IC50 of 1.79 µM and 0.92 µM (MTT) for LNCaP and PC3 tumor cells, respectively, and 5,7 higher for the Vero cells (IC50 = 7.14 µM), indicating preferential cytotoxicity to tumor cells. LQB-472 treatment also showed an increase in cell death through apoptosis. LQB-472 is known as pterocarpanoquinone-quinone because it has two <i>para</i>-naphthoquinone (1,4-naphthoquinone) groups, where an additional 1,4-benzoquinone ring was inserted between rings C and D of the LQB-118 structure. In conclusion, the structure-activity relationship analysis of the studied molecules indicates that the binding site and the position of the methoxy group in the molecule are crucial for the antitumor effect. The duplicity of the para-naphthoquinone group, observed in the LQB-472, was directly associated with the five times amplified effect observed concerning LQB-118 (4.6 µM). The results obtained with LQB-472 are quite promising and encourage the continuation of its pre-clinical studies due to its potential use in the treatment of prostate cancer.</p>

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Antitumor Potential of the Pterocarpanoquinone-Quinone LQB-472 in Prostate Cancer Cells

  • 期刊论文

  • 发表日期：

    2025年8月4日

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  • Thayssa G. Farias,
  • Rachell R. C. Thimoteo,
  • Felipe C. Demidoff,
  • Alcides J. M. da Silva,
  • Marcia S. dos Santos,
  • Paulo R. R. Costa,
  • Chaquip D. Netto,
  • Katia C. C. Sabino,
  • Graça Justo

摘要

Prostate cancer is among the most common in the world. Since it is a very resistant type of cancer, the search for new therapeutic alternatives becomes crucial. Aiming to research new molecules to treat prostate cancer, a set of five derivatives of the previously proven antiprostatic LQB-118 molecules were synthesized, and their in vitro antitumor action was screened by MTT and Trypan Blue dye exclusion assays. The cell cycle and cell death by apoptosis were analyzed using flow cytometry. The derivatives LQB-471, LQB-472, LQB-473, LQB-474, and LQB-475 cytotoxicities were analyzed in hormone-sensitive (LNCaP) and resistant (PC3) prostate tumor cell lines, as well as in the Vero non-tumor cell line. LQB-471, LQB-472, and LQB-474 induced cytotoxicity in both tumor cell lines, with LQB-472 being the most active, acting in a time and concentration-dependent manner in both prostate tumor lineages. In 72 h of incubation, LQB-472 showed IC50 of 1.79 µM and 0.92 µM (MTT) for LNCaP and PC3 tumor cells, respectively, and 5,7 higher for the Vero cells (IC50 = 7.14 µM), indicating preferential cytotoxicity to tumor cells. LQB-472 treatment also showed an increase in cell death through apoptosis. LQB-472 is known as pterocarpanoquinone-quinone because it has two para-naphthoquinone (1,4-naphthoquinone) groups, where an additional 1,4-benzoquinone ring was inserted between rings C and D of the LQB-118 structure. In conclusion, the structure-activity relationship analysis of the studied molecules indicates that the binding site and the position of the methoxy group in the molecule are crucial for the antitumor effect. The duplicity of the para-naphthoquinone group, observed in the LQB-472, was directly associated with the five times amplified effect observed concerning LQB-118 (4.6 µM). The results obtained with LQB-472 are quite promising and encourage the continuation of its pre-clinical studies due to its potential use in the treatment of prostate cancer.