| Overexpression of aldo-keto reductase 1C3(AKR1C3)in humans causes leukemia,and tyrosine kinases can cause cancer cell proliferation through signaling,resulting in leukemia.Therefore,AKR1C3 inhibitors and tyrosine kinase inhibitors(TKI)can be used to treat leukemia.Our group has obtained a novel candidate AKR1C3 inhibitor,2-(3-tertbutylphenylamino)-benzoic acid,through computer-aided drug design;tyrosine kinase inhibitors were selected from a generation of imatinib drug and a second-generation dasatinib drug.And such targeted anticancer drugs often have special biological activity and stability,and their presence has been detected in environmental media such as water,soil and organisms,becoming a new type of pollutant,and the environmental problems caused by them have become a hot research topic in recent years.In this study,the dominant algal species of waterwash,Microcystis aeruginosa,was selected as the model organism,with the aim of investigating the effects of a novel candidate AKR1C3 inhibitor and two tyrosine kinase inhibitors on the ecotoxicity and apoptosis profile of Microcystis aeruginosa.The biomass of the three drugs was consistent with a dose-time effect,with dasatinib showing a slight stimulatory effect at 6.6 mg/L.All three inhibitors affected the synthesis of chlorophyll a,carotenoids and soluble proteins in Microcystis aeruginosa;under 2-(3-tert-butylphenylamino)-benzoic acid stress,the production of ACP by Microcystis aeruginosa was stimulated at low concentrations,and under imatinib mesylate and dasatinib stress,it was The inhibition of ACP synthesis by imatinib mesylate was greater than that by dasatinib,and the above experiments indicated that the acute toxicity of imatinib mesylate was greater.In terms of antioxidant level and phycotoxin synthesis release,both 2-(3-tert-butylphenylamino)-benzoic acid and dasatinib can exhibit antioxidant capacity to some extent and have certain antioxidant level,the results of imatinib mesylate showed that the antioxidant capacity exhibited on the first and second day was inhibited,and imatinib mesylate under 48 h hour treatment with increasing concentration of MDA content increased and the ability to scavenge free radical ions weakened,further inducing cellular senescence more or even death.Both 2-(3-tert-butylphenylamino)-benzoic acid and dasatinib exhibited highly significant stimulation of algal cell synthesis of phycotoxin in the low concentration treatment group on day 8,and promoted the release of extracellular phycotoxin at all concentrations on days 4 and 8.In contrast,the effect of imatinib mesylate exhibited highly significant synthesis and release of extracellular phycotoxin on day 4,and at day 8,all concentrations exhibited The trend was consistent with the fourth day.At the level of apoptosis,Microcystis aeruginosa showed the greatest degree of apoptosis under imatinib mesylate stress at the experimental concentrations of the three drug treatments,which corresponded to the trend in the growth volume curve of its algal cells.The method of the above study can provide an important reference and some theoretical basis for the evaluation of human drug use. |
