lethality-bioassay-using-artemia-salina-l

Lethality Bioassay Using <em>Artemia salina</em> L.

Natural products have been used since ancient times to produce medicines. Nowadays, there are plenty of chemotherapeutic drugs obtained from natural ...

Universidade Lusófona de Humanidades e Tecnologias

Glioblastoma (GB) is the most malignant form of primary astrocytoma, accounting for more than 60% of all brain tumors in adults. Nowadays, due to the development of multidrug resistance causing relapses to the current treatments and the development of severe side effects resulting in reduced survival rates, new therapeutic approaches are needed. The genus  belongs to the Lamiaceae family and is known to be rich in abietane-type diterpenes, which possess antitumor activity. Specifically,  (Forssk.) Schweinf.  Sprenger has been documented for the use against brain tumors. Therefore, the aim of this work was to perform the bioguided isolation of compounds from the acetonic extract of  stems and to investigate the in vitro antiglioblastoma activity of the extract and its isolated constituents. After extraction, six fractions were obtained from the acetonic extract of  stems. In a preliminary biological screening, the fractions V and III showed the highest antioxidant and antimicrobial activities. None of the fractions were toxic in the  assay. We obtained different abietane-type diterpenes such as 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6β,7β-dihydroxyroyleanone (DiRoy), which was also in agreement with the HPLC-DAD profile of the extract. Furthermore, the antiproliferative activity was assessed in a glioma tumor cell line panel by the Alamar blue assay. After 48 h treatment, Roy exerted strong antiproliferative/cytotoxic effects against tumor cells with low IC values among the different cell lines. Finally, we synthesized a new fluorescence derivative in this study to evaluate the biodistribution of Roy. The uptake of BODIPY-7α-acetoxy-6β-hydroxyroyleanone by GB cells was associated with increased intracellular fluorescence, supporting the antiproliferative effects of Roy. In conclusion, Roy is a promising natural compound that may serve as a lead compound for further derivatization to develop future therapeutic strategies against GB.

Phytochemical Study and Antiglioblastoma Activity Assessment of  (Forssk.) Schweinf. ex Sprenger var. hadiensis Stems.

The enzyme PARP1 is an attractive target for cancer therapy, as it is involved in DNA repair processes. Several PARP1 inhibitors have been approved for clinical treatments. However, the rapid outbreak of resistance is seriously threatening the efficacy of these compounds, and alternative strategies are required to selectively regulate PARP1 activity. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter was recently identified. In this study, we explore the interaction of known G-quadruplex binders with the G-quadruplex structure found in the PARP gene promoter region. The results obtained by NMR, CD, and fluorescence titration, also confirmed by molecular modeling studies, demonstrate a variety of different binding modes with small stabilization of the G-quadruplex sequence located at the PARP1 promoter. Surprisingly, only pyridostatin produces a strong stabilization of the G-quadruplex-forming sequence. This evidence makes the identification of a proper (3+1) stabilizing ligand a challenging goal for further investigation.

Article	Year
Phytochemical Study and Antiglioblastoma Activity Assessment of (Forssk.) Schweinf. ex Sprenger var. hadiensis Stems. Molecules (Basel, Switzerland)\| PubMed ID: 35744938	2022
Exploring the Interaction of G-quadruplex Binders with a (3 + 1) Hybrid G-quadruplex Forming Sequence within the PARP1 Gene Promoter Region. Molecules (Basel, Switzerland)\| PubMed ID: 35897968	2022

Salvatore Princiotto

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