Atorvastatin and Nitrofurantoin Repurposed in the Context of Breast Cancer and Neuroblastoma Cells

Abstract

Chemotherapy still plays a central role in the treatment of cancer. However, it is often accompanied by off-target effects that result in severe side-effects and development of drug resistance. The aim of this work was to study the efficacy of different repurposed drugs on the viability of MCF-7 and SH-SY5Y breast cancer and neuroblastoma cells, respectively. In addition, combinations of these repurposed drugs with a classical chemotherapeutic drug (doxorubicin) were also carried out. The cytotoxic effects of the repurposed drugs were evaluated individually and in combination in both cancer cell lines, assessed by MTT assays and morphological evaluation of the cells. The results demonstrated that atorvastatin reduced the viability of both cell lines. However, nitrofurantoin was able to induce cytotoxic effects in MCF-7 cells, but not in SH-SY5Y cells. The combinations of the repurposed drugs with doxorubicin induced a higher inhibition on cell viability than the repurposed drugs individually. The combination of the two repurposed drugs demonstrated that they potentiate each other. Synergism studies revealed that the combination of doxorubicin with the two repurposed drugs was more effective in SH-SY5Y cells, compared to MCF-7 cells. Taken together, our preliminary study highlights the potential use of atorvastatin and nitrofurantoin in the context of breast cancer and neuroblastoma.

Synthesis, Antimicrobial, and Anticancer Activities of Novel Nitrofuran Derivatives

“…Step one involved the condensation of the commercially available isatin with hydrazine hydrate to provide the intermediate (1) in 91% global yield. Diverse precursors have been used to prepare diferent (Z)-3-hydrazonoindolin-2-ones [28,30]. In step 2, compound 1 underwent a second condensation step by refuxing with 5-nitro-2-furaldehyde using EtOH acidifed with glacial acetic acid as a solvent to aford the Schif base (2).…”

“…Considering the widespread resistance to the antimicrobial drugs used in current treatment protocols, we report herein the design and synthesis of new efcacious nitrofuran hybrids containing isatin for antimicrobial studies (Figure 5). Furthermore, several isatin and nitrofuran derivatives have been documented to display potent anticancer activity [28][29][30][31]. Terefore, the hybrid molecules were also screened as potential anticolon cancer agents.…”

Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical and Translational Neuropsychiatry

“…Therefore, the process of repurposing existing drugs for new applications, referred to as drug repurposing, offers a promising strategy for the development of novel and potent anticancer agents or adjuvants [ 58 , 93 , 94 , 95 ]. In this special issue, three articles were published that explored the potential of drug repurposing in the context of cancer and its associated challenges [ 96 , 97 , 98 ]. One article by Moura et al assessed the anticancer properties of atorvastatin, a medication used to reduce cholesterol levels, and nitrofurantoin, an antibiotic [ 96 ].…”

“…In this special issue, three articles were published that explored the potential of drug repurposing in the context of cancer and its associated challenges [ 96 , 97 , 98 ]. One article by Moura et al assessed the anticancer properties of atorvastatin, a medication used to reduce cholesterol levels, and nitrofurantoin, an antibiotic [ 96 ]. The authors tested the efficacy of repurposed drugs on breast cancer and neuroblastoma cells to determine their effectiveness, both individually and in combination with doxorubicin.…”

Positive Inotropic Agents in Cancer Therapy: Exploring Potential Anti-Tumor Effects

“…The importance of studies on new drugs for cancer treatment has grown significantly in recent decades due to its relevance [33]. Several works of our group have explored the cytotoxic effects of repurposed drugs and presented positive results regarding the cytotoxicity of some repurposed drugs, such as atorvastatin and nitrofurantoin in breast cancer and neuroblastoma [34] and CNS drugs in bladder cancer [35].…”