MEDICINAL ORGANIC CHEMISTRY GROUP

Pacheco, P. A. F., Ferreira, R. J. F., Fontinha, D., Sousa, C. C., Legac, J., Barcherini, V., Rosenthal, P. J., Prudêncio, M., Moreira, D. R. M., Santos, M. M. M., “Structural optimization of indolizinoindolones to obtain potent new antimalarials with dual stage activity”. European Journal of Medicinal Chemistry Reports, 2025, 14, 100258, https://doi.org/10.1016/j.ejmcr.2025.100258

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​Barros, H. L., Espadinha, L., Pinto, S. N., Ferreira, R. J. F., Loureiro, J. B., Silva, R., Saraiva, L., Maçôas, E., Santos, M. M. M., “Tryptophanol-derived oxazoloisoindolinone fluorescent probes for cellular localization studies of p53 activators”. Bioorganic Chemistry, 2024, 154, 107898, https://doi.org/10.1016/j.bioorg.2024.107898

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Vieira, P., Bettencourt , A.F., Panteli, E., Santos, C., Gonçalves, L. M. , Francisco, A.P., Ribeiro, I.A.C., “Exploring triazene derivative's antimicrobial activity and its incorporation onto 3D-printed coatings”.  Materials Today Chemistry, 2024, 38, 102133, https://doi.org/10.1016/j.mtchem.2024.102133

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Bento, C., Katz, M., Santos, M. M. M., Afonso, C. A. M. “Striving for Uniformity: A Review on Advances and Challenges to Achieve Uniform Polyethylene Glycol”, Org. Process Res. Dev. 2024, 28, 4, 860-890, doi:10.1021/acs.oprd.3c00428.

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Delgado, T., Pais, J. P., Pires, D., Estrada, F. G. A., Guedes, R. C., Anes, E., Constantino, L. "Development of New Drugs to Treat Tuberculosis Based on the Dinitrobenzamide Scaffold.", Pharmaceuticals. 2024, 17, 5, 559. https://doi.org/10.3390/ph17050559

Pais, J. P., Antoniuk O, Pires D, Delgado T, Fortuna A, Costa PJ, Anes E, Constantino L. "Synthesis, Activity, Toxicity, and In Silico Studies of New Antimycobacterial N-Alkyl Nitrobenzamides. Pharmaceuticals.", 2024, 17, 5, 608. https://doi.org/10.3390/ph17050608

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Pinho, J. O, Matias, M., Godinho-Santos, A., Amaral, J., Mendes, E., Perry, M.J., Francisco, A.P., Rodrigues, C.M.P., Gaspar, M. M.,  “A step forward on the in vitro and in vivo assessment of a novel nanomedicine against melanoma”. Int J Pharm, 2023 123011, ,  https://doi.org/10.1016/j.ijpharm.2023.123011

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Girst, G., Lopes, E. A., Gonçalves, L. M., Espadinha, M., Kúsz, N., Wang, H. C., Santos, M. M. M. *, Hunyadi, A. “Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells”, RSC Med. Chem. 2023, 14, 9, 1778-1786, doi: 10.1039/d3md00251a.

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Lopes, E. A., Santos, M. M. M., Mori, M. “Antimalarial drugs: what’s new in the patents?”, Expert Opin. Ther. Pat. 2023, 33 (3), 151-168, doi:10.1080/13543776.2023.2203814.

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Bahls, B.; Aljnadi, I.M.; Emídio, R.; Mendes, E.; Paulo, A. G-Quadruplexes in c-MYC Promoter as Targets for Cancer Therapy. Biomedicines 2023, 11, 969, doi:10.3390/biomedicines11030969.

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Barcherini, V.; Loureiro, J.B.; Sena, A.; Madeira, C.; Leandro, P.; Saraiva, L.; Antunes, A.M.M.; Santos, M.M.M. Metabolism-Guided Optimization of Tryptophanol-Derived Isoindolinone P53 Activators. Pharmaceuticals (Basel) 2023, 16, 146, doi:10.3390/ph16020146.

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Ferreira, R.; Pacheco, P. A. F.; Santos, M.M.M. Reativação Da P53 Usando Pequenas Moléculas Para Terapia Anticancerígena. Química 2023, 47, 30. https://b-quimica.spq.pt/files/files/BSPQ/74.pdf.

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Pinho, J.O.; Matias, M.; Marques, V.; Eleutério, C.; Fernandes, C.; Gano, L.; Amaral, J.D.; Mendes, E.; Perry, M.J.; Moreira, J.N.; Storm, G.; Francisco, A. P.; Rodrigues, C. M. P.; Gaspar, M. M.  Preclinical Validation of a New Hybrid Molecule Loaded in Liposomes for Melanoma Management. Biomed. Pharmacother. 2023, 157, 114021, doi:10.1016/j.biopha.2022.114021.

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Espadinha, M.; Lopes, E.A.; Marques, V.; Amaral, J.D.; dos Santos, D.J.V.A.; Mori, M.; Daniele, S.; Piccarducci, R.; Zappelli, E.; Martini, C.; Rodrigues, C.M.; Santos, M. M. M. Discovery of MDM2-P53 and MDM4-P53 Protein-Protein Interactions Small Molecule Dual Inhibitors. Eur. J. Med. Chem. 2022, 241, 114637, doi:10.1016/j.ejmech.2022.114637.

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Pais, J.P.; Policarpo, M.; Pires, D.; Francisco, A.P.; Madureira, A.M.; Testa, B.; Anes, E.; Constantino, L. Fluoroquinolone Derivatives in the Treatment of Mycobacterium Tuberculosis Infection. Pharmaceuticals (Basel) 2022, 15, 1213, doi:10.3390/ph15101213.

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Pais, J.P.; Magalhães, M.; Antoniuk, O.; Barbosa, I.; Freire, R.; Pires, D.; Valente, E.; Testa, B.; Anes, E.; Constantino, L. Benzoic Acid Derivatives as Prodrugs for the Treatment of Tuberculosis. Pharmaceuticals (Basel) 2022, 15, 1118, doi:10.3390/ph15091118.

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Mendes, E.; Bahls, B.; Aljnadi, I.M.; Paulo, A. Indoloquinolines as Scaffolds for the Design of Potent G-Quadruplex Ligands. Bioorg. Med. Chem. Lett. 2022, 72, 128862, doi:10.1016/j.bmcl.2022.128862.

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Lopes, E.A.; Mestre, R.; Fontinha, D.; Legac, J.; Pei, J.V.; Sanches-Vaz, M.; Mori, M.; Lehane, A.M.; Rosenthal, P.J.; Prudêncio, M.; Santos, M. M. M. Discovery of Spirooxadiazoline Oxindoles with Dual-Stage Antimalarial Activity. Eur. J. Med. Chem. 2022, 236, 114324, doi:10.1016/j.ejmech.2022.114324.

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Pacheco, P.A.F.; Santos, M.M.M. Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis. Molecules 2022, 27, 319, doi:10.3390/molecules27010319.

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Mendes, E.; Aljnadi, I.M.; Bahls, B.; Victor, B.L.; Paulo, A. Major Achievements in the Design of Quadruplex-Interactive Small Molecules. Pharmaceuticals (Basel) 2022, 15, 300, doi:10.3390/ph15030300.

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Loureiro, J.B.; Ribeiro, R.; Nazareth, N.; Ferreira, T.; Lopes, E.A.; Gama, A.; Machuqueiro, M.; Alves, M.G.; Marabini, L.; Oliveira, P.A.; Santos, M.M.M. Mutant P53 Reactivator SLMP53-2 Hinders Ultraviolet B Radiation-Induced Skin Carcinogenesis. Pharmacol. Res. 2022, 175, 106026, doi:10.1016/j.phrs.2021.106026.

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Mendes, R.M.; Francisco, A.P.; Carvalho, F.A.; Dardouri, M.; Costa, B.; Bettencourt, A.F.; Costa, J.; Gonçalves, L.; Costa, F.; Ribeiro, I.A.C. Fighting S. Aureus Catheter-Related Infections with Sophorolipids: Electing an Antiadhesive Strategy or a Release One? Colloids Surf. B Biointerfaces 2021, 208, 112057, doi:10.1016/j.colsurfb.2021.112057.

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Granada, M.; Mendes, E.; Perry, M.J.; Penetra, M.J.; Gaspar, M.M.; Pinho, J.O.; Serra, S.; António, C.T.; Francisco, A.P. Sulfur Analogues of Tyrosine in the Development of Triazene Hybrid Compounds: A New Strategy against Melanoma. ACS Med. Chem. Lett. 2021, 12, 1669–1677, doi:10.1021/acsmedchemlett.1c00252.

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Pinto, L.M.A.; Adeoye, O.; Thomasi, S.S.; Francisco, A.P.; Cabral-Marques, H. A Single-Step Multicomponent Synthesis of a Quinoline Derivative and the Characterization of Its Cyclodextrin Inclusion Complex. J. Mol. Struct. 2021, 1237, 130391, doi:10.1016/j.molstruc.2021.130391.

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Cadoni, E.; Magalhães, P.R.; Emídio, R.M.; Mendes, E.; Vítor, J.; Carvalho, J.; Cruz, C.; Victor, B.L.; Paulo, A. New (Iso)Quinolinyl-Pyridine-2,6-Dicarboxamide G-Quadruplex Stabilizers. A Structure-Activity Relationship Study. Pharmaceuticals (Basel) 2021, 14, 669, doi:10.3390/ph14070669.

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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.

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Espadinha, M.; Barcherini, V.; Gonçalves, L.M.; Molins, E.; Antunes, A.M.M.; Santos, M.M.M. Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma. Pharmaceuticals (Basel) 2021, 14, 208, doi:10.3390/ph14030208.

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Raposo, L.R.; Silva, A.; Silva, D.; Roma-Rodrigues, C.; Espadinha, M.; Baptista, P.V.; Santos, M.M.M.; Fernandes, A.R. Exploiting the Antiproliferative Potential of Spiropyrazoline Oxindoles in a Human Ovarian Cancer Cell Line. Bioorg. Med. Chem. 2021, 30, 115880, doi:10.1016/j.bmc.2020.115880.

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Barcherini, V.; Almeida, J.; Lopes, E.A.; Wang, M.; Magalhães e Silva, D.; Mori, M.; Wang, S.; Saraiva, L.; Santos, M.M.M. Potency and Selectivity Optimization of Tryptophanol‐derived Oxazoloisoindolinones: Novel P53 Activators in Human Colorectal Cancer. ChemMedChem 2021, 16, 250–258, doi:10.1002/cmdc.202000522.

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Lopes, E.A.; Santos, M.M.M.; Mori, M. Pharmacological Treatment of Malaria. In Topics in Medicinal Chemistry; Topics in medicinal chemistry; Springer International Publishing: Cham, 2021; pp. 219–240 doi.org/10.1007/7355_2021_125.

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Pinto, L.M.A.; Adeoye, O.; Thomasi, S.S.; Francisco, A.P.; Carvalheiro, M.C.; Cabral-Marques, H. Preparation and Characterization of a Synthetic Curcumin Analog Inclusion Complex and Preliminary Evaluation of in Vitro Antileishmanial Activity. Int. J. Pharm. 2020, 589, 119764, doi:10.1016/j.ijpharm.2020.119764.

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Ghosh, R.; Vitor, J.B.; Mendes, E.; Paulo, A.; Acharya, P.C. Stereoselective Synthesis of Spirooxindole Derivatives Using One-Pot Multicomponent Cycloaddition Reaction and Evaluation of Their Antiproliferative Efficacy. ACS Omega 2020, 5, 27332–27343, doi:10.1021/acsomega.0c03675.

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Ramos, H.; Calheiros, J.; Almeida, J.; Barcherini, V.; Santos, S.; Carvalho, A.T.P.; Santos, M.M.M.; Saraiva, L. SLMP53-1 Inhibits Tumor Cell Growth through Regulation of Glucose Metabolism and Angiogenesis in a P53-Dependent Manner. Int. J. Mol. Sci. 2020, 21, 596, doi:10.3390/ijms21020596.

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Adeoye, O.; Bártolo, I.; Conceição, J.; da Silva, A.B.; Duarte, N.; Francisco, A.P.; Taveira, N.; Cabral-Marques, H. Pyromellitic Dianhydride Crosslinked Soluble Cyclodextrin Polymers: Synthesis, Lopinavir Release from Sub-Micron Sized Particles and Anti-HIV-1 Activity. Int. J. Pharm. 2020, 583, 119356, doi:10.1016/j.ijpharm.2020.119356.

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Espadinha, M.; Viejo, L.; Lopes, R.M.R.M.; Herrera-Arozamena, C.; Molins, E.; dos Santos, D.J.V.A.; Gonçalves, L.; Rodríguez-Franco, M.I.; Ríos, C. de L.; Santos, M.M.M. Identification of Tetracyclic Lactams as NMDA Receptor Antagonists with Potential Application in Neurological Disorders. Eur. J. Med. Chem. 2020, 194, 112242, doi:10.1016/j.ejmech.2020.112242.

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Zwergel, C.; Fioravanti, R.; Stazi, G.; Sarno, F.; Battistelli, C.; Romanelli, A.; Nebbioso, A.; Mendes, E.; Paulo, A.; Strippoli, R.; Tripodi, M.; Pechalrieu, D.; Arimondo, P. B.; De Luca, T.; Del Bufalo, D.; Trisciuoglio, D.; Altucci, L.; Valente, S.; Mai, A. Novel Quinoline Compounds Active in Cancer Cells through Coupled DNA Methyltransferase Inhibition and Degradation. Cancers (Basel) 2020, 12, 447, doi:10.3390/cancers12020447.

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Gomes, A.S.; Ramos, H.; Gomes, S.; Loureiro, J.B.; Soares, J.; Barcherini, V.; Monti, P.; Fronza, G.; Oliveira, C.; Domingues, L.; Bastos, M.; Dourado, D. F. A. R.; Carvalho, A. L.; Romão, M. J.; Pinheiro, B.; Marcelo, F.; Carvalho, A.; Santos, M. M. M.; Saraiva, L.  SLMP53-1 Interacts with Wild-Type and Mutant P53 DNA-Binding Domain and Reactivates Multiple Hotspot Mutations. Biochim. Biophys. Acta Gen. Subj. 2020, 1864, 129440, doi:10.1016/j.bbagen.2019.129440.

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Lopes, E.A.; Santos, M.M.M. Synthesis of Spirooxindoles by Multicomponent Reactions. Synthetic Approaches to Nonaromatic Nitrogen Heterocycles 2020, 225–247, doi.org/10.1002/9781119708841.ch9.

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Espadinha, M.; Conway, S.J.; Santos, M.M.M. PPIs as Therapeutic Targets for Anticancer Drug Discovery: The Case Study of MDM2 and BET Bromodomain Inhibitors. In Small Molecule Drug Discovery; Elsevier, 2020; pp. 267–288. doi.org/10.1016/B978-0-12-818349-6.00010-8.

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Lopes, E.A.; Gomes, S.; Saraiva, L.; Santos, M.M.M. Small Molecules Targeting Mutant P53: A Promising Approach for Cancer Treatment. Curr. Med. Chem. 2020, 26, 7323–7336, doi:10.2174/0929867325666181116124308.

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Gomes, S.; Bosco, B.; Loureiro, J.B.; Ramos, H.; Raimundo, L.; Soares, J.; Nazareth, N.; Barcherini, V.; Domingues, L.; Oliveira, C.; Bisio, A.; Piazza, S.; Bauer, M. R.; Brás, J. P.; Almeida, M. I.; Gomes, C.; Reis, F.; Fersht, A. R.; Inga, A.; Santos, M. M. M.; Saraiva, L. SLMP53-2 Restores Wild-Type-like Function to Mutant P53 through Hsp70: Promising Activity in Hepatocellular Carcinoma. Cancers (Basel) 2019, 11, 1151, doi:10.3390/cancers11081151.

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Francisco, A.P.; Mendes, E.; Santos, A.R.; Perry, M.J. Anticancer Triazenes: From Bioprecursors to Hybrid Molecules. Curr. Pharm. Des. 2019, 25, 1623–1642, doi:10.2174/1381612825666190617155749.

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Amaral, J.D.; Silva, D.; Rodrigues, C.M.P.; Solá, S.; Santos, M.M.M. A Novel Small Molecule P53 Stabilizer for Brain Cell Differentiation. Front. Chem. 2019, 7, doi:10.3389/fchem.2019.00015.

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Mendes, E.; Cadoni, E.; Carneiro, F.; Afonso, M.B.; Brito, H.; Lavrado, J.; Dos Santos, D.J.V.A.; Vítor, J.B.; Neidle, S.; Rodrigues, C.M.P.; 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, 1325–1328, doi:10.1002/cmdc.201900243.

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Espadinha, M.; Lourenço, N.M.T.; Sobral, L.; Antunes, R.; Santos, M.M.M. A More Sustainable Process for Preparation of the Muscarinic Acetylcholine Antagonist Umeclidinium Bromide. ChemMedChem 2018, 13, 2053–2056, doi:10.1002/cmdc.201800387.

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Raimundo, L.; Espadinha, M.; Soares, J.; Loureiro, J.B.; Alves, M.G.; Santos, M.M.M.; Saraiva, L. Improving Anticancer Activity towards Colon Cancer Cells with a New P53‐activating Agent. Br. J. Pharmacol. 2018, 175, 3947–3962, doi:10.1111/bph.14468.

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Faustino, C.; Francisco, A.P.; Isca, V.M.S.; Duarte, N. Cytotoxic Stilbenes and Derivatives as Promising Antimitotic Leads for Cancer Therapy. Curr. Pharm. Des. 2019, 24, 4270–4311, doi:10.2174/1381612825666190111123959.

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Espadinha, M.; Barcherini, V.; Lopes, E.A.; Santos, M.M.M. An Update on MDMX and Dual MDM2/X Inhibitors. Curr. Top. Med. Chem. 2018, 18, 647–660, doi:10.2174/1568026618666180604080119.

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Duarte, A.R.; Cadoni, E.; Ressurreição, A.S.; Moreira, R.; Paulo, A. Design of Modular G‐quadruplex Ligands. ChemMedChem 2018, 13, 869–893, doi:10.1002/cmdc.201700747.

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Francisco, A.P.; Paulo, A. Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules. Curr. Med. Chem. 2017, 24, 4873–4904, doi:10.2174/0929867323666160829145055.

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Ribeiro, C.J.A.; Nunes, R.C.; Amaral, J.D.; Gonçalves, L.M.; Rodrigues, C.M.P.; Moreira, R.; Santos, M.M.M. Spirotriazoline Oxindoles: A Novel Chemical Scaffold with in Vitro Anticancer Properties. Eur. J. Med. Chem. 2017, 140, 494–509, doi:10.1016/j.ejmech.2017.09.037.

 

Sousa, A.; Santos, F.; Gaspar, M.M.; Calado, S.; Pereira, J.D.; Mendes, E.; Francisco, A.P.; Perry, M.J. The Selective Cytotoxicity of New Triazene Compounds to Human Melanoma Cells. Bioorg. Med. Chem. 2017, 25, 3900–3910, doi:10.1016/j.bmc.2017.04.049.

 

Nunes, R.C.; Ribeiro, C.J.A.; Monteiro, Â.; Rodrigues, C.M.P.; Amaral, J.D.; Santos, M.M.M. In Vitro Targeting of Colon Cancer Cells Using Spiropyrazoline Oxindoles. Eur. J. Med. Chem. 2017, 139, 168–179, doi:10.1016/j.ejmech.2017.07.057.

 

Soares, J.; Espadinha, M.; Raimundo, L.; Ramos, H.; Gomes, A.S.; Gomes, S.; Loureiro, J.B.; Inga, A.; Reis, F.; Gomes, C.; Santos, M. M. M. DIMP53-1: A Novel Small-Molecule Dual Inhibitor of P53-MDM2/X Interactions with Multifunctional P53-Dependent Anticancer Properties. Mol. Oncol. 2017, 11, 612–627, doi:10.1002/1878-0261.12051.

 

Mariz, I.F.A.; Pinto, S.; Lavrado, J.; Paulo, A.; Martinho, J.M.G.; Maçôas, E.M.S. Cryptolepine and Quindoline: Understanding Their Photophysics. Phys. Chem. Chem. Phys. 2017, 19, 10255–10263, doi:10.1039/c7cp00455a.

 

Espadinha, M.; Dourado, J.; Lajarin-Cuesta, R.; Herrera-Arozamena, C.; Gonçalves, L.M.D.; Rodríguez-Franco, M.I.; de los Rios, C.; Santos, M.M.M. Optimization of Bicyclic Lactam Derivatives as NMDA Receptor Antagonists. ChemMedChem 2017, 12, 537–545, doi:10.1002/cmdc.201700037.