Degree: Doctor

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CIQUP

Bio

Alexandra Gaspar graduated from the Faculty of Pharmacy, University of Porto 2007. She completed her MSc studies at the University of Lisbon and, in 2013, concluded her PhD studies at the Faculty of Sciences, University of Porto. Her scientific career focuses on public health and well-being, with an emphasis on the discovery and development of innovative therapeutic solutions resourcing to new bioactive chemical compounds. Spanning over 15 years in the field of medicinal chemistry, Alexandra Gaspar has actively contributed to multiple funded research projects in medicinal chemistry and drug discovery. She was the principal investigator of the "Trojan Horse" project (EXPL/MED-QUI/1156/2021) and has also collaborated on several other funded research projects. Her scientific outputs include co-authoring 3 national patents, one international patent application, 3 chapter books (one as the corresponding author), more than 50 peer-reviewed papers (4 as the corresponding author, 11 as the first author, and 10 as co-first author), and 15 conference proceedings. Alexandra Gaspar’s works have garnered several scientific distinctions, resulting in an h-index of 24 and a citation count of over 2500 (from WoS). In 2022, she was recognized as one of the "World's Top 2% Scientists" by Stanford University (USA) in the sub-field of medicinal chemistry. Alexandra Gaspar has also actively participated in various initiatives to contribute to the research community and share knowledge globally. She has been involved in Erasmus initiatives such as the Blended Intensive Programme (BIP) and COST Actions. She has organized scientific conferences, served as a moderator, and presented over 30 oral presentations and more than 70 poster communications at international and national scientific events. Additionally, she takes part in (co)supervising undergraduate and graduate students and contributes as a lecturer in various curricular units, such as Medicinal Chemistry and advanced methods in Structural Analysis. She also serves as a referee and guest editor for several journals in the field of Medicinal Chemistry.

Publications
Showing 5 latest publications. Total publications: 56
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1. 4-Oxoquinolines and monoamine oxidase: When tautomerism matters, Mesiti, F; Maruca, A; Silva, V; Rocca, R; Fernandes, C; Remiao, F; Uriarte, E; Alcaro, S; Gaspar, A Borges, F in EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2021, ISSN: 0223-5234,  Volume: 213, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1016/j.ejmech.2021.113183 P-00T-CGB
Abstract 4-Oxoquinoline derivatives have been often used in drug discovery programs due to their pharmacological properties. Inspired on chromone and 4-oxoquinoline chemical structure similarity, a small series of quinoline-based compounds was obtained and screened, for the first time, toward human monoamine oxidases isoforms. The data showed the N-(3,4-dichlorophenyl)-1-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide 10 was the most potent and selective MAO-B inhibitor (IC50 = 5.30 +/- 0.74 nM and SI: >= 1887). The data analysis showed that prototropic tautomerism markedly influences the biological activity. The unequivocal characterisation of the quinoline tautomers was performed to understand the attained data. To our knowledge, there have been no prior reports on the characterisation of quinolone tautomers by 2D NMR techniques, namely by H-1-N-15 HSQC and H-1-N-15 HMBC, which are proposed as expedite tools for medicinal chemistry campaigns. Computational studies on enzyme-ligand complexes, obtained after MM-GBSA calculations and molecular dynamics simulations, supported the experimental data.
2. Mapping Chromone-3-Phenylcarboxamide Pharmacophore: Quid Est Veritas?, Mesiti, F; Gaspar, A Chavarria, D Maruca, A; Rocca, R; Martins, EG; Barreiro, S; Silva, R; Fernandes, C; Gul, S; Keminer, O; Alcaro, S; Borges, F in JOURNAL OF MEDICINAL CHEMISTRY, 2021, ISSN: 0022-2623,  Volume: 64, 
Article,  Indexed in: crossref, wos  DOI: 10.1021/acs.jmedchem.1c00510 P-00V-5MW
Abstract Chromone-3-phenylcarboxamides (Crom-1 and Crom-2) were identified as potent, selective, and reversible inhibitors of human monoamine oxidase B (hMAO-B). Since they exhibit some absorption, distribution, metabolism, and excretion (ADME)-toxicity liabilities, new derivatives were synthesized to map the chemical structural features that compose the pharmacophore, a process vital for lead optimization. Structure-activity relationship data, supported by molecular docking studies, provided a rationale for the contribution of the heterocycle's rigidity, the carbonyl group, and the benzopyran heteroatom for hMAO-B inhibitory activity. From the study, N-(3-chlorophenyl)-4H-thiochromone-3-carboxamide (31) (hMAO-B IC50 = 1.52 +/- 0.15 nM) emerged as a reversible tight binding inhibitor with an improved pharmacological profile. In in vitro ADME-toxicity studies, compound 31 showed a safe cytotoxicity profile in Caco-2, SH-SY5Y, HUVEC, HEK-293, and MCF-7 cells, did not present cardiotoxic effects, and did not affect P-gp transport activity. Compound 31 also protected SH-SY5Y cells from iron(III)-induced damage. Collectively, these studies highlighted compound 31 as the first-in-class and a suitable candidate for in vivo preclinical investigation.
3. The synthesis, crystal structure and Hirshfeld analysis of 4-(3,4-dimethylanilino)-N-(3,4-dimethylphenyl)quinoline-3-carboxamide, Gomes, LR; Low, JN; Borges, F; Gaspar, A Mesiti, F in ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, 2020, ISSN: 2056-9890,  Volume: 76, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1107/s2056989020000298 P-00R-R9P
Abstract The structure of the title quinoline carboxamide derivative, C26H25N3O, is described. The quinoline moiety is not planar as a result of a slight puckering of the pyridine ring. The secondary amine has a slightly pyramidal geometry, certainly not planar. Both intra- and intermolecular hydrogen bonds are present. Hirshfeld surface analysis and lattice energies were used to investigate the intermolecular interactions.
4. Searching for new cytotoxic agents based on chromen-4-one and chromane-2,4-dione scaffolds, Gaspar, A Mohabbati, M; Cagide, F Razzaghi Asl, N; Miri, R; Firuzi, O; Borges, F in RESEARCH IN PHARMACEUTICAL SCIENCES, 2019, ISSN: 1735-5362,  Volume: 14, 
Article,  Indexed in: authenticus, crossref, scopus, wos  DOI: 10.4103/1735-5362.251855 P-00Q-84P
Abstract Cancer is a major cause of death worldwide and novel anticancer agents for its better management are much needed. Benzopyrone-based compounds, such as chromones, possess several distinctive chemical and biological properties, of which the cytotoxicity against cancer cells seems to be prominent. In this study, two series of compounds based on chromen-4-one (3-10) and chromane-2,4-dione (11-18) scaffolds were synthesized in moderate/high yields and evaluated for cytotoxicity against HL-60, MOLT-4, and MCF-7 cancer cells using MTT assay. In general, the compounds exhibited moderate cytotoxic effects against the cancer cell lines, among which, a superior potency could be observed against MOLT-4 cells. Chroman-2,4dione (11-18) derivatives had overall higher potencies compared to their chromen-4-one (3-10) counterparts. Compound 13 displayed the lowest IC50 values against HL-60 (IC50, 42.0 +/- 2.7 mu M) and MOLT-4 cell lines (IC50, 24.4 +/- 2.6 mu M), while derivative 11 showed the highest activity against MCF-7 cells (IC50, 68.4 +/- 3.9 04). In conclusion, this study provides important information on the cytotoxic effects of chromone derivatives. Benzochroman-2,4-dione has been identified as a promising scaffold, which its potency can be modulated by tailored synthesis with the aim of finding novel and dissimilar anticancer compounds.
5. The chemistry toolbox of multitarget-directed ligands for Alzheimer's disease, Mesiti, F; Chavarria, D Gaspar, A Alcaro, S; Borges, F in EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, ISSN: 0223-5234,  Volume: 181, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1016/j.ejmech.2019.111572 P-00Q-Y5C
Abstract The discovery and development of multitarget-directed ligands (MTDLs) is a promising strategy to find new therapeutic solutions for neurodegenerative diseases (NDs), in particular for Alzheimer's disease (AD). Currently approved drugs for the clinical management of AD are based on a single-target strategy and focus on restoring neurotransmitter homeostasis. Finding disease-modifying therapies AD and other NDs remains an urgent unmet clinical need. The growing consensus that AD is a multifactorial disease, with several interconnected and deregulated pathological pathways, boosted an intensive research in the design of MTDLs. Due to this scientific boom, the knowledge behind the development of MTDLs remains diffuse and lacks balanced guidelines. To rationalize the large amount of data obtained in this field, we herein revise the progress made over the last 5 years on the development of MTDLs inspired by drugs approved for AD. Due to their putative therapeutic benefit in AD, MTDLs based on MAO-B inhibitors will also be discussed in this review.