In the search of new uses for old drugs

Prof.T. Theophanides theophan@central.ntua.gr J. Anastassopoulou, S. Kella & K. Xenos In the search of new uses for old drugs

DRUG DISPOSAL • PHARMACEUTICALS • 1. Organic : Aspirin, etc. • 2.Inorganic : Boric Acid, etc. • 3. Organometallic : Metal salts, Metal- complexes

A lot of materials change their properties even at ambient temperature. • Experimental observation of these changes is difficult due to their very low rate of change, which results in so small physicochemical changes that are, generally, immeasurable even by the most sensitive analytical techniques

We have checked with FT-IR Spectroscopy to see if there was a change in the IR spectrum of an expired drug compared to the normal drug. • We found that the FT-IR spectrum did not change at all and the two spectra were identical. • It is accepted that the IR spectrum of a material is the “finger print” of that material. • Then what is the change that takes place in the expired drug?

FT-IR spectra of Aspirin. Red: normal Aspirin and Blue: expired Aspirin

Comparing compounds and diseases will help find new drugs from a molecular point of view from the publicly available database. • A potential compatibility between numerous drugs and diseases for which those drugs had never been before thought to be beneficial has been found. • This research was performed at Stanford School of Medicine “Math.com”.

Finding New Uses for Old Drugs • In another case, the drugs were categorized based on genetic background and not on the affected organs. • But such leaps do occur in the medical world, albeit typically by accident instead of by systematic search.

Notable examples include: • Sildenafil(Viagra) repositioned from a candidate for hypertension to a successful drug for erectile dysfunction • Gemcitabine(Gemzar) switched from use as an antiviral candidate to a successful anticancer agent • Finasterideexpanded use from prostate cancer (Proscar) to hair loss (Propecia) • Thalidomide (Thalidomid) repositioned from a discontinued antiemetic drug to a successful cancer therapeutic • Hydroxychloroquine(Plaquenil). Expanded use from an antiparasitic to an approved antiarthritic agent

Recycling old drugs in new appearances • The chance finding that a drug designed for one purpose might fit the gap…is discovering new uses for old drugs or teaching an old drug new tricks! • This could be a less costly process of obtaining pharmaceuticals for other new diseases.

Pharmaceutical used in this study • Hydrocortisone : Solu-Cortef Solu-Cortef(A) contains the active ingredient hydrocortisone sodium succinate (B) which is a type of compound known as a corticosteroid. Corticosteroids are derivatives of the corticosteroid hormones cortisol and aldosterone that are produced naturally by the adrenal glands

Hydrocortisone : Solu-Cortef • This medication is used to treat various conditions such as: • Severe allergic reactions, blood diseases, breathing problems, certain cancers, eye diseases, intestinal disorders, and skin diseases. • Hydrocortisone is a corticosteroid hormone (glucocorticoid).

Hydrocortisone Metal-complexes C25H33O8MCl∙5Η2Ο

Results • Preliminary experiments showed that these hydrocortisone metal-complexes could be used for treating melanoma much better than the original drug (found from melanoma tests) . • The metals used were life metal ions, such as Na+, K+, Mg2+, Ca2+, Fe2+, Mn2+, Zn2+, Sn2+and others, which would be mineralized as metal ions in the electrolytes of the body. • The transformation of unused drugs to organometallic adducts could lead to new uses of old drugs.

Fourier Transform Infrared Spectra of hydrocortisone and its metal-complexes in the region 4000- 2500 cm-

Fourier Transform Infrared Spectra of hydrocortisone and its metal-complexes in the region (2000- 400 cm -1)

Conclusions • The transformation of unused old drugs to organometallic-adducts could lead to more active new drugs (reactivation of old drugs). • This novel method of recuperation of unused old drugs could be made with the non-toxic life metals, such as: Na+, K+, Mg2+, Ca2+, Fe2+, Mn2+, Zn2+, Sn2+and others. • This new way of metallation of non-disposed old drugs leads to a useful novel recycling method.

Old drugs Metallation Re-activated drugs Thank You

In the search of new uses for old drugs