dual inhibitor of the human epidermal growth factor receptor 2 and epidermal growth factor receptor, was recently approved by the FDA (2017) and by the EMA (2018) for the treatment of breast cancer. Finally, a number of further Michael acceptor drug candidates are currently under clinical investigation for pharmacotherapy of inflammation and cancer. In this review, we focus on the pharmacology of NFA and other Michael acceptor drugs, summarizing their potential as an emerging class of future antiphlogistics and adjuvant in tumor therapeutics.

Endogenous nitro-fatty acids (NFA) are potent electrophilic lipid mediators that exert biological effects in vitro and in vivo via selective covalent modification of thiol-containing target proteins. The cytoprotective, anti-inflammatory, and anti-tumorigenic effects of NFA in animal models of disease caused by targeted protein nitroalkylation are a valuable basis for the development of future anti-phlogistic and anti-neoplastic drugs. Considering the complexity of diseases and accompanying comorbidities there is an urgent need for clinically effective multifunctional drugs. NFA are composed of a fatty acid backbone containing a nitroalkene moiety triggering Michael addition reactions. However, less is known about the target-specific structure–activity relationships and selectivities comparing different NFA targets. Therefore, we analyzed 15 NFA derivatives and compared them with the lead structure 9-nitro-oleic acid (9NOA) in terms of their effect on NF-κB (nuclear factor kappa B) signaling inhibition, induction of Nrf-2 (nuclear factor erythroid 2-related factor 2) gene expression, sEH (soluble epoxide hydrolase), LO (lipoxygenase), and COX-2 (cyclooxygenase-2) inhibition, and their cytotoxic effects on colorectal cancer cells. Minor modifications of the Michael acceptor position and variation of the chain length led to drugs showing increased target preference or enhanced multi-targeting, partly with higher potency than 9NOA. This study is a significant step forward to better understanding the biology of NFA and their enormous potential as scaffolds for designing future anti-inflammatory drugs.

Biogenic Silver nanoparticles (AgNPs) are one of the most fascinating nanomaterials used in biomedical purposes. In the current study, we biosynthesized AgNPs using Arthrospira platensis, Microcystis aeruginosa and Chlorella vulgarisactive metabolites and evaluate their efficacy against breast cancer. The recovered AgNPs was characterized using scanning and transmission electron microscopy (SEM and TEM). The safety usage of bio-AgNPs was tested in-vitro on PBMCs cells and in-vivo. The obtained results indicated the safety usage of bio-AgNPs at concentration 0.1 mg/ml on PBMCs cells and 1.5mg/ml on the tested Albino mice. The bio-AgNPs displayed dose-dependent cytotoxicity (0.1 mg/ml) against HepG-2, CaCO-2 and MCF-7 cell lines via ROS induction and arresting treated cells in G0/G1 and sub G0 phases. In addition, Arthrospira bio-AgNPs treatment induced cellular apoptosis in breast cancer cells via the down regulation of survivin, MMP7, TGF and Bcl2 genes expressions. Upon Arthrospira bio-AgNPs treatment, a great delay in tumor growth and prolonged survival were recorded in breast cancer mice model. Furthermore, after Arthrospira bio-AgNPs treatment, a great reduction in Ki 67 protein marker from 60% to be 20% and was recorded and an elevation in Caspase 3 protein levels was recorded in treated groups with percentage 65% comparing with 45% in Doxorubicin treated groups.