breast-pathology-medchem-2018-posters

9 / 22

Page 69
Notes:
Journal of Clinical & Experimental Pathology | ISSN: 2161-0681 | Volume 8
Breast Pathology and Cancer Diagnosis
6th World Congress and Expo on
July 25-26, 2018 | Vancouver, Canada
Medicinal Chemistry and Rational Drugs
20 th International Conference on
&
Design, synthesis and biological evaluation of novel celastrol derivatives as potent and selective
cytotoxic compounds
Jorge A R Salvador1,2, Sandra AC Figueiredo1,2, VanessaI, S Mendes2,3, Roldán Cortés4, Marta Cascante4 and Jorge A R Salvador1,2
1University of Coimbra, Portugal
2Centre for Neuroscience and Cell Biology, Portugal
3Biocant - Parque Tecnológico de Cantanhede, Portugal
4University of Barcelona, Spain
Triterpenoids comprise a large and structurally diverse class of natural products. Among these, celastrol is one of the most
active antitumour compounds. It has been reported to be highly active against a wide variety of tumours and to affect
multiple cellular pathways. Therefore, celastrol is an ideal candidate for designing lead compounds for the development of new
anticancer agents. In this communication we report the synthesis of novel celastrol derivatives as potent and selective cytotoxic
compounds. Celastrol analogues, including carbamate derivatives, were designed and synthesised, and their anticancer activity
was evaluated using different human cancer cell lines. Moreover, these new compounds were subjected to a preliminary
structure–activity relationship study.The best derivatives were selected considering their best activity onmalignant cell viability,
combined with the highest selectivity between cancer cells and non-malignant fibroblasts. It was performed preliminary
mechanistic studies with the best compound, which indicated a important cytotoxic effect on SKOV-3 human ovarian cancer
cells (IC50 = 0.54 µM). Additionally, the results suggested that this compound presented an antiapoptotic activity, mediated
mainly through activation of extrinsic apoptotic pathway. Furthermore, our results demonstrated the potential of this derivative
as a new agent for combinatorial drug therapy for ovarian cancer.
Biography
Jorge A R Salvador has a degree in Pharmaceutical Sciences, a Master degree in Organic & Tecnological Chemistry, and a Ph.D. in Pharmaceutical Chemistry from
the University of Coimbra in collaboration with the University of York, UK. He has a position as Full Professor at Faculty of Pharmacy of the University of Coimbra – Portugal.
Author and co-author of over 90 publications in peer-review journals, 10 book chapters and 10 patents, two of them have been granted in US. Co-founder of the
company CHEM4PHARMA, Lda,
Jorge A R Salvador et al., J Clin Exp Pathol 2018, Volume 8
DOI: 10.4172/2161-0681-C3-052