Two sets of benzimidazole derivatives were synthesised and tested in vitro for activity against promastigotes of Leishmania tropica and L. infantum. Most of the tested compounds resulted active against both Leishmania species, with IC values in the low micromolar/sub-micromolar range. Among the set of 2-(long chain)alkyl benzimidazoles, whose heterocyclic head was quaternised, compound 8 resulted about 100-/200-fold more potent than miltefosine, even if the selectivity index (SI) versus HMEC-1 cells was only moderately improved. In the set of 2-benzyl and 2-phenyl benzimidazoles, bearing a basic side chain in position 1, compound 28 (2-(4-chlorobenzyl)-1-lupinyl-5-trifluoromethylbenzimidazole) was 12-/7-fold more potent than miltefosine, but exhibited a further improved SI. Therefore, compounds 8 and 28 represent interesting hit compounds, susceptible of structural modification to improve their safety profiles.
Two diazotrophic cyanobacteria (Anabaena cylindrica PCC 7122 and Nostoc sp. PCC 7120) were cultivated to produce cyanophycin, a nitrogen reserve compound, under nitrogen fixing conditions. In preliminary continuous experiments, Nostoc sp. was shown to be more efficient, accumulating a higher amount of cyanophycin and showing a greater capability to fix atmospheric nitrogen in the biomass (67 mgN d−1 of fixed nitrogen per liter of culture). The operating conditions were then optimized to maximize the cyanophycin productivity: the effect of incident light intensity, residence time and nitrogen availability were investigated. Nitrogen availability and/or pH played a major role with respect to biomass production, whereas phosphorus limitation was the main variable to maximize cyanophycin accumulation. In this way, it was possible to achieve a stable and continuous production of cyanophycin (CGP) under diazotrophic conditions, obtaining a maximum cyanophycin productivity of 15 mgCGP L−1 d−1.
Key points
• Diazotrophic cyanobacteria produce stable amount of cyanophycin in continuous PBR.
• Nostoc sp. proved to be more efficient in producing cyanophycin than Anabaena sp.
• P deprivation is the major variable to increase cyanophycin productivity in continuous.
Triple-negative breast cancer—defined by the absence of oestrogen/progesterone receptors and human epidermal growth factor receptor 2 expression—is a complex and heterogeneous type of tumour characterised by poor prognosis, aggressive behaviour and lack of effective therapeutic strategies. The identification of new biomarkers and molecular signatures is leading to development of new therapeutic strategies including immunotherapy, targeted therapy and antibody-drug conjugates (ADCs). Against a background where chemotherapy has always been considered the standard of care, evolution towards a precision medicine approach could improve TNBC clinical practice in a complex scenario, with many therapeutic options and new drugs. The aim of this review was to focus on emerging therapeutic targets and their related specific therapy, discussing available and emerging drugs, underlining differences in approval by American and European regulatory authorities and showing the future perspective in the large number of ongoing clinical trials.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.