Preclinical Development of Seriniquinones as Selective Dermcidin Modulators for the Treatment of Melanoma

Autor(es)

Hirata, Amanda S. ; La Clair, James J. ; Jimenez, Paula C. ; Costa-Lotufo, Leticia Veras ; Fenical, William

• Tipo de documento: Artigo Científico
• Fonte: MARINE DRUGS; v. 20, n. 5, p. 13-pg., 2022-05-01.

Resumo

The bioactive natural product seriniquinone was discovered as a potential melanoma drug, which was produced by the as-yet-undescribed marine bacterium of the rare genus Serinicoccus. As part of a long-term research program aimed at the discovery of new agents for the treatment of cancer, seriniquinone revealed remarkable in vitro activity against a diversity of cancer cell lines in the US National Cancer Institute 60-cell line screening. Target deconvolution studies defined the seriniquinones as a new class of melanoma-selective agents that act in part by targeting dermcidin (DCD). The targeted DCD peptide has been recently examined and defined as a "pro-survival peptide" in cancer cells. While DCD was first isolated from human skin and thought to be only an antimicrobial peptide, currently DCD has been also identified as a peptide associated with the survival of cancer cells, through what is believed to be a disulfide-based conjugation with proteins that would normally induce apoptosis. However, the significantly enhanced potency of seriniquinone was of particular interest against the melanoma cell lines assessed in the NCI 60-cell line panel. This observed selectivity provided a driving force that resulted in a multidimensional program for the discovery of a usable drug with a new anticancer target and, therefore, a novel mode of action. Here, we provided an overview of the discovery and development efforts to date. (AU)

• Processo FAPESP: 20/06613-8 - Caracterização do mecanismo de ação da seriniquinona em células de Melanoma resistentes ao vemurafenibe
• Beneficiário: Amanda Soares Hirata
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/17177-6 - Abordagem integrada na prospecção sustentável de produtos naturais marinhos: da diversidade a substâncias anticâncer
• Beneficiário: Leticia Veras Costa Lotufo
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático