The aim of the study was to evaluate the antifungal activity of extracts of 10 plant species used in traditional Uruguayan medicine against the phytopathogenic fungus Alternaria spp. The plants were selected on the basis of their reported ethnobotanical uses. Aqueous, saline buffer and acid extracts of different plant species were screened in vitro for their antifungal activity against Alternaria spp. For the antifungal evaluation we used a microspectrophotometric assay. Minimal inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of the extracts were determined. Three solvents were assayed on different tissues of the plants and among the 29 evaluated extracts, 31% of the extracts inhibited growth, similar to the effects of a chemical fungicide. Acid extracts of the plants were more effective than the aqueous or buffer extracts against Alternaria spp. The MIC values of the extracts were determined ranging between 1.25 and 25 µg mL -1 . The MFC values of the extracts ranged between 1.25 µg mL -1(Rosmarinus officinalis L.) and 10 µg mL -1 (Cynara scolymus L.). MICs and MFCs values obtained from leaves (Salvia officinalis L. and R. officinalis) and seeds extracts (Salvia sclarea L.) were quite comparable to values obtained with the conventional fungicide captan (2.5 µg mL -1 ). The extracts of Salvia sclarea, S. officinalis and R. officinalis could be considered as potential sources of antifungal compounds for treating diseases in plants. These extracts showed maximum activity, even at very low concentrations, and the same fungicide effects as chemical fungicide. We conclude from this that these extracts exhibit amazing fungicidal properties that support their traditional use as antiseptics.

No abstract

Proteolysis targeting chimeras (PROTACs) are a class of small molecules designed to target proteins for degradation. Their novel and unique modes of action provide PROTACs with the potential for their application in the management of both solid and hematologic malignancies. Since its initial discovery, the technology of targeted protein degradation, especially in the form of PROTACs, has had significant advances. A number of PROTACs have entered a late stage of preclinical development. Several of them are either in phase 1/2 clinical trials or approaching approval for initial clinical evaluation. This article discusses the preclinical and clinical findings of PROTACs of clinically relevant protein targets in cancer.

Direct blockade of KRAS driver mutations in colorectal cancer (CRC) has been challenging. Targeting SOS1, a guanine nucleotide exchange factor, has arisen as an attractive approach for KRAS-mutant CRC. Here, we describe the development of novel SOS1 degraders and their activity in patient-derived CRC organoids (PDO). The design of these degraders as proteolysis-targeting chimera was based on the crystal structures of cereblon and SOS1. The synthesis used the 6-and 7-OH groups of a quinazoline core as anchor points to connect lenalidomide. Fifteen compounds were screened for SOS1 degradation. P7 was found to have up to 92% SOS1 degradation in both CRC cell lines and PDOs with excellent specificity. SOS1 degrader P7 demonstrated superior activity in inhibiting CRC PDO growth with an IC 50 5 times lower than that of SOS1 inhibitor BI3406. In summary, we developed new SOS1 degraders and demonstrated SOS1 degradation as a feasible therapeutic strategy for KRAS-mutant CRC.