UNA4CAREER
This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement Nยบ 847635.
920234. Group of Bioactive Heterocycles (BIOHET)
Department of Chemistry in Pharmaceutical Sciences
Facultad de Farmacia
The BIOHET group is currently developing several projects in the area of drug discovery, with emphasis in neurodegenerative diseases but also working on neglected infectious diseases. It is also active in the field of green chemistry applied to medicinal chemistry projects, since efficient and sustainable synthetic access are key factors for a drug candidate (https://www.researchgate.net/profile/J_Carlos_Menendez). BIOHET has received the grade “Excellent” in a recent evaluation by the Spanish Research Agency, and is funded by several regional and national-level Spanish agencies, being also a member of two COST Actions. In the last 10 years, the group has generated 175 scientific publications and 26 PhD theses, with another 8 being in progress at the moment. We have active collaborations with many European laboratories that provide suitable places for temporary scientific placements where the candidate can learn techniques complementary to the ones employed in our group, including Professor Maria Laura Bolognesi (Bologna University), Dr. Claudio Santi (Perugia University), Professor Arasu Ganesan (University of East Anglia), Professor James C. Anderson (University College London), Dr. Evelina Colacino (Montpellier University). The group also has some long-standing collaborations with pharmaceutical companies such as Rovi and has generated 5 patents in recent years.
The BIOHET group occupies five research laboratories. It has standard organic chemistry lab equipment, a freeze dryer, cryostats, vacuum pumps, two Parr reactors, an ozone generator, two ball mills, an ultrasound probe, two focused microwave reactors, a flash chromatograph, three HPLC instruments, a polarimeter, FT- IR and UV-visible spectrophotometers (including a multi-well reader), two spectrofluorimeters with optical fiber probe, multi-well reader, two plate fluorimeters, one absorbance plate reader, a thermobalance, PCR systems, an automated electrophoresis system, CO2 incubator, two inverted microscopes, two image analyzers, a cell culture room with two vertical laminar flow hoods, a flow cytometer, two Western-blot systems and an autoclave. We have access to Central Research Services at UCM, providing 6 NMR instruments (250 to 700 MHz), mass spectrometry, elemental analysis, X-ray diffraction, confocal microscopy and animal facilities.
Neurodegenerative diseases are the main health-related challenge that our societies will need to face in the future. Thus, Alzheimer’s disease, the most prevalent neurodegenerative disease, affects about 50 million patients and is projected to reach a prevalence of 150 million patients in 2050. Neurodegenerative diseases are one of the most challenging fields of drug discovery and the prospects for success in this area using the current methods are very low. This most likely happens because the diseases are too complex to be treated by targeting a single physiological process, as failed drug candidates do. The fact that several large pharmaceutical companies have stopped their research on neurodegenerative diseases makes the academic investigation of innovative approaches to drug discovery in this area even more relevant.
This scenario calls for the introduction of new drug design strategies. One that is attracting much attention in recent years is the replacement of the «one drug-one target» paradigm by the multitarget approach, where drugs are intentiaonally designed to modulate at least two different molecular targets and which is more likely to succeed in the case of disorders that have complex, multifactorial pathological mechanisms such as neurodegenerative diseases. In this context, heterocyclic small molecules targeting some of the multiple factors involved in AD such as amyloid aggregation, hyperphosphorylation of tau protein leading to neurofibrillary tangles, oxidative stress, neuroinflammation, neurotransmitter deficiency, neuronal calcium homeostasis and mitochondrial dysfunction will be designed with the aid of computational techniques, synthesized using sustainable methodologies and tested pharmacologically.
