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Cyclam-based compounds as a novel class of antibacterial and antitumoral agents
Luis G. Alves * 1 , Adhan Pilon 2, 3 , Sergi Rodriguez-Calado 4 , João F. Portel 5, 6 , Olga Ferreira 7, 8 , Sílvia A. Sousa 6 , Andreia Valente 2 , Julia Lorenzo 4 , Elisabete R. Silva 7, 8 , Ana M. Martins 5 , Jorge H. Leitão 6
1  Centro de Química Estrutural, Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento, Av. Rovisco Pais 1, 1049-003 Lisboa, Portugal
2  Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal
3  Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal
4  Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
5  Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal
6  Instituto de Bioengenharia e Biociências, Instituto Superior Técnico, Universidade de Lisboa Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal
7  Biosystems & Integrative Sciences Institute, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal
8  Centro de Recursos Naturais e Ambiente, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal

Published: 30 October 2019 by MDPI AG in 5th International Electronic Conference on Medicinal Chemistry session Posters
10.3390/ECMC2019-06292
Abstract:

Cyclams are macrocyclic polyamines which medical interest was fueled by the therapeutic potential of a bicyclam derivative in HIV infection, inflammatory diseases, cancer and stem-cell mobilization.[1] Taking advantage of the biocompatibility, the high metal chelation stability constants and the possibility of N-functionalization of the cyclam backbone, a variety of compounds have been explored in a wide range of medicinal applications.[2] The use of cyclams and cyclam-based complexes as antimicrobial and antitumoral agents has been described in recent years. In particular, trans-disubstituted cyclam salts revealed to be active antibacterial agents against both Gram-positive and Gram-negative bacteria.[3,4]

In the field of anticancer applications, several attempts are being made, mostly with CuII complexes, envisaging their use as 64/67Cu radionuclides.[5] Recently, we found that trans-disubstituted cyclam derivatives and their CuII and FeIII complexes display relevant antitumoral activity against HeLa cancer cell lines.[6] To the best of our knowledge, this is the first report on an iron-cyclam compound tested as anticancer agent.

[1] De Clercq, E., Nat. Rev. Drug Discov. 2003, 2, 581–587

[2] Liang, X.; Sadler, P. J., Chem. Soc. Rev. 2004, 33, 246-266

[3] Yu, M.; Nagalingam, G.; Ellis, S.; Martinez, E.; Sintchenko, V.; Spain, M.; Rutledge, P. J.; Todd, M. H.; Triccas, J. A., J. Med. Chem. 2016, 59, 5917–5921

[4] Alves, L. G.; Pinheiro, P. F.; Feliciano, J. R.; Dâmaso, D. P.; Leitão, J. H.; Martins, A. M., Int. J. Antimicrob. Agents 2017, 49, 646-649

[5] Cai, Z.; Anderson, C. J., J. Label. Compd. Radiopharm. 2014, 57, 224–230

[6] Pilon, A.; Lorenzo, J.; Rodriguez-Calado, S.; Adão, P.; Martins, A. M.; Valente, A.; Alves, L. G., ChemMedChem, 2019, 14, 770-778

Keywords: Cyclam, Azamacrocycles, Antibacterials, Antitumorals, E. coli, S. aureus, HeLa cells
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