Repurposing the anti-malarial drug, quinacrine: new anti-colitis properties

Abstract

BackgroundUlcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with an increased risk of colorectal cancer in 8-10 years after disease onset. Current colitis treatment strategies do not offer a cure for the disease, but only treat the symptoms with limited success and dangerous side-effects. Also, there is no preventive treatment for either UC or colorectal cancer. Quinacrine is an anti-malarial drug with versatile use in the treatment of diseases involving inflammatory response such as rheumatoid arthritis and lupus erythematosus. It also has putative anti-cancer effect. Quinacrine's anti-inflammatory, anti-oxidant properties, and anti-tumorigenic properties make it a potential small molecule preventive agent for both UC and associated colorectal cancer.ResultsThere were obvious changes in the CDI, histology, and inflammatory load in quinacrine-treated groups in a dose and time dependent manner in both models of UC, induced by chemical or haptenating agent.MethodsWe tested quinacrine at two different doses as a colitis treatment agent in two mouse models of UC - the dextran sulfate sodium and oxazolone. The clinical disease index (CDI), histological changes of the colon, levels of inflammatory markers (Cox-2, iNOS, p53) and overall health vitals were evaluated.ConclusionsWe demonstrate that quinacrine successfully suppresses colitis without any indication of toxicity or side-effects in two mouse models of UC.

A Quinacrine Analogue Selective Against Gastric Cancer Cells: Insight from Biochemical and Biophysical Studies

“…In this connection, further biophysical studies to derive quantitative 4 b –DNA binding parameters are now in course, and the results will be timely reported. Taken together, our findings reinforce the therapeutic value of repurposing QN‐based scaffolds for cancer, as already highlighted by others . Compound 4 b , in particular, seems to be a valuable template for further structural optimization toward selective and potent candidates and is worthy of further preclinical and clinical profiling as a novel agent of higher safety and specificity for gastric cancer.…”

“…It has also been used as a nonsurgical female sterilization method . As such, QN and its analogues can be taken as prototypical examples of “polyspecific” therapeutic scaffolds that possess tremendous potential for repurposing, as recently acknowledged by others …”

“…[17] As such, QN and its analogues can be taken as prototypical exampleso f" polyspecific" therapeutic scaffolds that possess tremendousp otential for repurposing, as recently acknowledged by others. [18] Our group has been working on the chemical modification of classical antimalarials, [7] such as primaquine, [19] chloroquine, [20] and QN, [21] with the aim to improvet heir antimalarial properties, and we found that the N-cinnamoyl derivatives of the latter two compounds (i.e.,d erivatives 3 and 4)w ere potent dual-stage antimalarial leads. In connection with the above and in light of the well-known anticancer potential of chloroquine and QN, as well as of our own findings regarding the antiproliferativep roperties of chloroquine derivatives 3, [22] we have now evaluated the in vitro activity of N-cinnamoyl QN derivative 4 against the MKN-28, Caco-2, MCF-7, and HFF-1 cell lines and unveiled the antiproliferativep otential of these compounds.…”

Repurposed quinacrine synergizes with cisplatin, reducing the effective dose required for treatment of head and neck squamous cell carcinoma

“…Quinacrine, also known as mepacrine, was initially utilized as an antimalarial agent as early as the 1930s and is considered safe, with only minimal side effects, such as headaches and gastrointestinal upset [7]. Quinacrine has also been proposed as a treatment for numerous other indications, from colitis [8] to prion disease [9]. Vassey et al (1955) [10] first assessed quinacrine as an anticancer agent in mice bearing several types of tumor, such as fibrosarcoma and carcinoma.…”

Looking for the best anti-colitis medicine: A comparative analysis of current and prospective compounds

“…Quinacrine has a long history of successful applications for the treatment of malaria, tape-worm infections, giardiasis and systemic lupus erythematosus, possesses antioxidant properties, and has efficacy against autoimmune disorders, such as rheumatoid arthritis with rare, but mild side effects [ 33 – 39 ]. We have shown that quinacrine successfully suppresses colitis without any indication of toxicity or side effects in two mouse models of UC [ 40 ].…”