Conferencias “Targeting drug resistance in cancer stem cells – Hedgehog pathway inhibitors – Taepeenin D” y “Abietane diterpenes – high value natural precursors for the development of new antimicrobial agents”
Comments (0) Fecha: martes 31 de octubre 10hs.
Lugar: Aula de Postgrado B, Edificio de Ciencias Políticas, Campus UCC
Disertante: Dr. Constantinos Athanassopoulos de la Universidad de Patras, Grecia.
Breve resumen de las conferencias (ver además archivos adjuntos):
Targeting drug resistance in cancer stem cells – Hedgehog pathway inhibitors – Taepeenin D
Cancer stem cells (CSCs) are a subpopulation of cancer cells with high clonogenic capacity and ability to reform parental tumors upon transplantation.
Several types of CSCs have shown resistance to chemotherapy and therefore they have been “accused” for causing tumor relapse. In the last decade many efforts have been made to design molecules, able to specifically target CSCs and to differentiate them or sensitize them to therapy. Among the different potential targets a special attention has been payed to the “Hedgehog pathway (Hh)”, which has emerged as a favourable target to address drug resistance in CSCs. Up to now a variety of natural, natural-derived (e.g. Cyclopamine) and synthetic origin molecules (e.g. Sonidegib, Vismodegib) have shown Hh inhibitory activity. Inhibitors of Gli1, the terminal effector of the pathway, are anticipated to evade drug resistance and to display fewer side effects than inhibitors targeting Smothened protein (Smo). Inspired by the Gli-mediated transcription inhibitor Taepeenin D we performed synthesis and evaluation of a series of analogues, which has led to key structure–activity relationships for this natural product. The information derived from this research will be discussed in the lecture.
Abietane diterpenes – high value natural precursors for the development of new antimicrobial agents
Abietanes are a family of naturally occurring diterpenoids with a highly diverse repertoire of associated bioactivities. They have generated significant interest from the medicinal and pharmacological communities since they exhibit anticancer, antiviral, antifungal and antibacterial activity. Especially the latter is potentially valuable in the battle against the antimicrobial resistance and imminent antibiotic shortage.
Recent results of Prof. Carpinella’s group demonstrated that an extract from Lepechinia meyenii exhibited an outstanding selectivity against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains. Bioguided fractionation led to the isolation of carnosol and rosmanol as its active principles with MIC values ranging from 9 to 62 and 15 to 125 μg/ml, respectively.
Prompted from these results and aiming at the development of new and more effective antimicrobial agents we synthesised a library of abietane analogues, using carnosic and abietic acid as the natural precursors, suitable for structure-activity relationship studies (SARS). Two promising compounds with MIC values ranging from 4 to 15 and 32 to 125 μg/ml against multi-resistant bacteria, were identified from the abietic acid derivatives. Very interesting results regarding the structural elements responsible for the activity improvement were obtained. A second generation of derivatives, as well as, the evaluation of the carnosic acid derivatives are in progress. The results obtained will be discussed in detail.
Antecedentes:
Prof. C.M. Athanassopoulos obtained his Diploma in Chemistry and his Ph.D in Organic Chemistry from the Chemistry Department, University of Patras in 1991 and 2003, respectively.
He has received three European Union fellowships in the frame of Human Capital & Mobility Program for research at the University of Calabria, Cosenza ITALY where he acquired skills in modern mass spectrometry analytical techniques and at the University of Minho, Braga, PORTUGAL. Later he received a scholarship from the Greek State Scholarship’s Foundation (IKY) for Postdoctoral research at the University of Patras and another one from the Norwegian Research Council for Postdoctoral research at the University of Bergen, Norway. He has delivered invited talks in the Universities of Calabria (IT), Bergen (NO) Insubria (IT) and Paul Sabatier (FR).
He has been teaching as visiting professor at Paul Sabatier’s, Toulouse, France (2017) and he won another visiting professorship at La Sapienza University, Rome, Italy to be performed in 2018.
He has supervised 22 diploma, 9 MSc and 3 PhD theses.
He is active member or management committee member substitute of 3 COST actions (NATCHEMDRUGS, MUTALIG, STEMCHEM).
He is member of the Royal Society of Chemistry (UK), the American Chemical Society (USA), the American Society for Mass Spectrometry (USA) and the Association of Greek Chemists.
He is co-author in 40 original research papers in international peer reviewed journals and over 400 citations.
