Saltar ao contido principal
Páxinas persoais  »  Eduardo Marcelo Sobarzo Sanchez

Research Topics

 

MEDICINAL CHEMISTRY IN NATURAL PRODUCTS

 

Our research in the scope of the natural products, it is been a powerful tool for combating several diseases like cancer and other pathological disorder, having contributed to get and to understand all the mechanism involved onto the formation of anticancer and anti-infective drugs as well as on Central Nervous System (CNS). Thus, "oxoisoaporphines" (7H-dibenzo[de,h]quinolin-7-one) are a small group of isoquinoline alkaloids that have shown an important chemical characteristic as antidepressive pro-drugs. In this sense, these alkaloids that bearing a nitrogen atom and a carbonyl group at C-1 and C-7 respectively, they have demostrated with several chemical structures, either total or partially hydrogenated, a high and selective ability to the inhibition of the isoform A of the human monoamine oxidase (h-MAO-A) in nanomolar range, according to the IC50 value. This unusual pharmacological property does not reported in the current bibliography due to that this type of pharmacological behaviour only had been found in certain amphetamine derivatives. This type of compound is a psychostimulant drug that is known to produce increased wakefulness and focus in association with decreased fatigue and appetite. Amphetamine is chemically related to methamphetamine and lisdexamfetamine, a class of potent drugs that act by increasing levels of dopamine and norepinephrine in the brain, inducing euphoria. The next chemical structures of "oxoisoaporphine" and all derivatives are shown as follows:

 
ESTRUCTURAS QUIMICAS 2
      
The next video shows to neural level the effects of the depression, and the impact on the human behaviour when is disease affects to our familiar environment.
 

 

 

In the other hand, recently oxoisoaporphine derivatives have shown a high grade of effectivity against some diseases called "from third world". Thus, Malaria and Leishmaniasis are two most significant parasitic diseases endemic in these regions and result in high rates of mortality and pose an additional socio-economic burden. Being short of effective immunoprophylaxis; relevant preventive sanitary measures and pharmacological approaches are needed to empower the undesirable effects of these diseases. Current antiparasitic chemotherapy is expensive, has undesirable side effects, or is marginally effective due to the problem of resistance. Collaboration of molecular biology and drug discovery approaches are required, which could lead to identification of new drug targets for efficient chemotherapeutic intervention. 

  

SUPRAMOLECULAR CHEMISTRY IN CYCLODEXTRINS

 

The supramolecular chemistry of cyclodextrins (CDs) has been widely used in pharmaceutical formulations of drugs to increase their water solubility (e.g. itraconazole) and stability (e.g.PGE1), to mask odor (garlic oil) and flavor, to perform a drug release control (loteprednol) and to favor their absorption (e.g. piroxicam). In most cases such formulations are based on unmodified CDs mixed with the corresponding drug. When a large increase in water solubility is desired sometimes dimethyl- or hydroxypropyl-β-CD is used.

 

In our first studies related with β-CD derivatives with some aromatic compounds as naphtho-quinolinones and coumarins, the experimental data shown an excellent incorporation of both type of compounds, with a regioselectivity of enter and incorporation constant (Ks) highest expected. However, this first step is the beginning to apply it to supramolecular systems with chromophore, which can be detected by UV-light when the guest-compound is incorporated inside CD.  
Thus, 3-phenyl-coumarin derivatives have been tested as potentially anti-Parkinson drugs, due to its selectivity in the nanomolar IC50 values range (http://www.sciencedirect.com/s). Such compounds have the chemical structure of resveratrol, known antioxidant, anti-inflammatory substance found in red wine. Further studies of resveratrol revealed that it helps prevent blood clots by keeping blood vessels open and pliable. However, the low solubility of the 3-phenyl-coumarin in aqueous medium, it would facilitate the carrier through blood brain barrier (BBB) by using cyclodextrin in the CNS. In this case, DIME-ß-CD showed to be the better carrier system, whilst HP-ß-CD would not have major difference with the previous one.

  

Our preliminary studies are based in the synthesis of these artificial vesicles that incorporate certain chromophore such as oxoisoaporphine or naphtho-quinolinones in the supramolecular framework, and once that modified synthetic CD can be obtained, these supramolecular systems will be joined to the Liposomes to carry drugs with high affinity by CD, but containing several CD in one artificial vesicle.

  

LIPOSOMAS