Maria M. M. Santos

Medicinal Organic Chemistry

Our research is focused on the design and synthesis of small molecules for relevant therapeutic targets. To achieve these goals, novel chemical methodologies are developed and applied to library synthesis, while focusing on structure-activity relationships, metabolic stability studies and identification of the possible metabolites for the most promising leads.


This line of research is focused on the discovery of novel and more selective anticancer drugs by designing and synthesising small molecules that target the tumor suppressor protein p53, as well as G4 structures in oncogene promoter regions of human cancer cells. Ongoing funded projects: PTDC/QUI-QOR/29664/2017 and PTDC/QUI-QOR/1304/2020.

Infectious Diseases

Alternatives to effectively treat tuberculosis and malaria are urgently needed. In our group we have been developing with success ester prodrugs of pyrazinoic acid that addressed efficiently pyrazinamide resistance in M. tuberculosis, and small molecules with dual stage activity for blood and liver stages of malaria. Ongoing funded project: PTDC/SAU-INF/28080/2017.

Therapeutic tools

This line of research is focused on maximizing the specificity and targetability of our hit compounds. In collaboration with the group of Advanced Technologies for Drug Delivery we are associating our most promising hits with nanodelivery systems. Ongoing funded project: PTDC/MED-QUI/31721/2017.

Valente E, Testa B, Constantino L. Activation of benzoate model prodrugs by mycobacteria. Comparison with mammalian plasma and liver hydrolysis. Eur J Pharm Sci. 2021, 162:105831. DOI: 10.1016/j.ejps.2021.105831.
Barcherini V, Almeida J, Lopes EA, Wang M, Magalhães e Silva D, Mori M, Wang S, Saraiva L, Santos MMM. Potency and selectivity optimization of tryptophanol‐derived oxazoloisoindolinones: Novel p53 activators in human colorectal cancer. ChemMedChem 2020, 15. DOI: 10.1002/cmdc.202000522
Espadinha M, Viejo L, Lopes R, Herrera-Arozamena C, Molins E, dos Santos DJVA, Gonçalves L, Rodríguez-Franco MI, de los Rios C, Santos MMM. Identification of tetracyclic lactams as NMDA receptor antagonists with potential application in neurological disorders. Eur. J. Med. Chem. 2020, 194, 11242. DOI: 10.1016/j.ejmech.2020.112242.
INVENTORS: Nuno Torres Lourenço, Luis Sobral, Rafael Antunes, Maria Santos, Margarida Espadinha; TITLE: Process for the preparation of Umeclidinium bromide; APPLICANTS: HOVIONE SCIENTIA LIMITED; PUBLICATION NUMBER: US20190263814; APPLICATION NUMBER: 16349404; PUBLICATION DATE: 29.08.2019; Also published as AU2017357653; CA3043554; CN110167931; EP3538524; IL266589; IN201917020855; JP2020500846; PT109740
Mendes E, Cadoni E, Carneiro F, Afonso MB, Brito H, Lavrado J, dos Santos DJVA, Vítor JB, Neidle S, Rodrigues CMP, Paulo A. Combining 1,3-ditriazolylbenzene and quinoline to discover a new G-quadruplex-interactive small molecule active against cancer stem-like cells. ChemMedChem 2019, 14: 1325-28. DOI: 10.1002/cmdc.201900243.

Maria M. M. Santos

Group Leader


Phone: (+351) 217946400 (Ext. 14329)/ (+351) 217946451

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Faculdade de Farmácia da Universidade de Lisboa | Av. Professor Gama Pinto
1649-003 Lisboa | Portugal

Phone | +351 217 946 400
Fax | +351 217 946 470
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