Protective potential of thymoquinone against cadmium, arsenic, and lead toxicity: A short review with emphasis on oxidative pathways.

Heavy metals are among the most important environmental pollutions used in various industries. Their extensive use has increased human susceptibility to different chronic diseases. Toxic metal exposure, especially cadmium, arsenic, and lead, causes oxidative damages, mitochondrial dysfunction, and genetic and epigenetic modifications. Meanwhile, thymoquinone (TQ) is an effective component of Nigella sativa oil that plays an important role in preventing the destructive effects of heavy metals. The present review discusses how TQ can protect various tissues against oxidative damage of heavy metals. This review is based on the research reported about the protective effects of TQ in the toxicity of heavy metals, approximately the last 10 years (2010-2021). Scientific databases, including Scopus, Web of Science, and PubMed, were searched using the following keywords either alone or in combination: cadmium, arsenic, lead, TQ, and oxidative stress. TQ, as a potent antioxidant, can distribute to cellular compartments and prevent oxidative damage of toxic metals. However, depending on the type of toxic metal and the carrier system used to release TQ in biological systems, its therapeutic dosage range may be varied.

Synthesis, Molecular Dynamics Simulation, and In-vitro Antitumor Activity of Quinazoline-2,4,6-triamine Derivatives as Novel EGFR Tyrosine Kinase Inhibitors.

Background: Developing a potent and safe scaffold is challenging in anti-cancer drug discovery. Objectives: The study focused on developing novel series of compounds based on the inhibition of epidermal growth factor receptor tyrosine kinase (EGFR-TK) as one of the most promising compounds in cancer therapy. Methods: In this study, a novel series of quinazoline-2,4,6-triamine derivatives were designed and synthesized through intramolecular C-H activation reaction of para-nitro aniline, trichloroacetonitrile, and isocyanides employing a one-pot reaction. Results: The in-vitro antitumor activities of the compounds which showed acceptable inhibitory effects were investigated against breast (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines by employing MTT assay. All compounds had the most negligible cytotoxicity toward normal fibroblast human cell lines. Based on structural and thermodynamics analysis results, it was found that Met 769 is a key residue in interaction with all inhibitors through the formation of hydrogen bonds with high occupancies with the amine group on the quinazoline ring of inhibitors. Also, there was a good consistency between calculated ΔG binding and experimental IC50 values of compounds 10d, 10e, and erlotinib. Conclusions: Compound 10e had an extensive range of antitumor activity on three diverse cell lines comparable with erlotinib and doxorubicin reference drugs. Also, compound 10d showed selective cytotoxicity against cancerous lung cells (A-549). On the other side, computational studies confirmed that Met 769 is a crucial residue in interaction with all inhibitors.