| Full text | |
| Author(s): |
Hirata, Amanda S.
;
La Clair, James J.
;
Jimenez, Paula C.
;
Costa-Lotufo, Leticia Veras
;
Fenical, William
Total Authors: 5
|
| Document type: | Journal article |
| Source: | MARINE DRUGS; v. 20, n. 5, p. 13-pg., 2022-05-01. |
| Abstract | |
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) | |
| FAPESP's process: | 20/06613-8 - Characterization of seriniquinone mechanism of action in vemurafenibe resistant Melanoma cells |
| Grantee: | Amanda Soares Hirata |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds |
| Grantee: | Leticia Veras Costa Lotufo |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |