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Nitrofuran drugs. (a) Furazolidone, (b) Nitrofurantoin, (c) Nitrofurazone, (d) Furaltadone.
Source publication
In this work, six novel 4-aryl-2-[2-((5-nitrofuran-2-yl)methylene)hydrazinyl] thiazole derivatives (2a-f) were synthesized starting from 5-nitro-2-furaldehyde diacetate by using Hantzsch thiazole synthesis. The antimicrobial activity of the title compounds were screened against five Gram positive bacteria B. cereus, E. faecalis, S. aureus, S. epide...
Citations
... Design of the new NFZ analogs preserved the essential pharmacologic features present in NF drugs (Fig. 3). This included firstly the 5-nitro group which is attached to furyl ring that is critical for both anticancer and antimicrobial activities [32,41] as its deletion results in compounds with diminished activity [32]. Besides, the metabolic studies of NFZ proved the significant reduction of nitrofuryl group into toxic metabolic products that covalently bind to proteins and DNA causing disruption of normal cellular processes [20]. ...
Drug repurposing has gained much attention as a cost-effective strategy that plays an exquisite role in identifying undescribed biological activities in clinical drugs. In the present work, we report the repurposing of the antibacterial drug nitrofurazone (NFZ) as a potential anticancer agent against CaCo-2, MDA-MB 231 and HepG-2 cancer cell lines. Novel series of nitrofurazone analogs was then designed considering the important pharmacologic features present in NFZ. Synthesis and biological evaluation of the target compounds revealed their promising anticancer activities endowed with antimicrobial potential and possessing better lipophilicity than NFZ. Compound 7, exclusively, inhibited the growth of all tested cancer cells more potently than NFZ with the least cytotoxicity against normal cells, displaying anti Gram-positive bacterial activities and antifungal potential. Analysis of the stereo-electronic properties of compound 7 via investigating the energies of HOMO, LUMO, HOMO-LUMO energy gap and MEP maps demonstrated its high reactivity and the expected molecular mechanism of action through reduction of the 5-nitrofuryl moiety. Data of the bioactivity studies indicated that the potent anticancer activity of 7 is mainly through increasing intracellular ROS levels and induction of apoptosis via significantly down-regulating the expression of Bcl-2 while up-regulating BAX, p53 and caspase 3 expression levels. Compound 7 potently inhibited the cellular expression levels of antioxidant enzymes GPx and GR compared to NFZ. Antioxidant enzymes kinetic studies and blind molecular docking simulations disclosed the mechanistic and structural aspects of the interaction between 7 and both GR and GPx. Thus, the successful discovery of 7 as a potential dual anticancer-antimicrobial nitrofurazone analog might validate the applicability of drug repurposing strategy in unravelling the unrecognized bioactivity of the present conventional drugs, besides furnishing the way towards more optimization and development studies.
