I studied Pharmacy in the University of Seville, in the south of Spain. After that, I didi one first MSc in Molecular Biology, at CEA in Grenoble (France). However, I realized that I was more interested in chemistry. For this reason, I decided to specialzed in Medicinal Chemistry and Pharmaceutical Innovation with another MSc at the University Grenoble Alpes (France).
In 2019, I received my Ph.D. in Medicinal Chemistry from the University of Franche-Comté in France. My work in the laboratory of Prof. Lhassane Ismaili focused on the synthesis of multi-targeting ligands, using the Ugi and Hantzsch multicomponent reaction, to target different factors involved in Alzheimer’s disease as potential therapeutics. I joined Prof. Glenn lab at Stanford University where I am interested in the synthesis of broad-spectrum antivirals that target the host PI-kinases.
PhD, University of Franche-Comté, France, Medicinal Chemistry (2019)
MSc, University of Grenoble Alpes, France, Medicinal Chemistry (2016)
MSc, CEA of Grenoble, France, Molecular Biology (2015)
Degree, University of Seville, Spain, Pharmacy (2014)
Synthesis of Hantzsch Adducts as Cholinesterases and Calcium Flux inhibitors, Antioxidants and Neuroprotectives
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2020; 21 (20)
We report herein the design, synthesis, biological evaluation, and molecular modelling of new inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), able to block Ca+2 channels also showing antioxidant and neuroprotective activities. The new MTDL, dialkyl 2,6-dimethyl-4-(4-((5-aminoalkyl)oxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate 3a-p, have been obtained via Hantzsch reaction from appropriate and commercially available precursors. Pertinent biological analysis has prompted us to identify MTDL 3h [dimethyl-4-(4-((5-(4-benzylpiperidin-1-yl)pentyl)oxy)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate] as an attractive inhibitor of AChE (1.8 μM) and BuChE (2 μM), Ca+2 channel antagonist (47.72% at 10 μM), and antioxidant (2.54 TE) agent, showing significant neuroprotection 28.68% and 38.29% against H2O2, and O/R, respectively, at 0.3 μM, thus being considered a hit-compound for further investigation in our search for anti-Alzheimer's disease agents.
View details for DOI 10.3390/ijms21207652
View details for Web of Science ID 000585603400001
View details for PubMedID 33081112
View details for PubMedCentralID PMC7589057
Triazolopyridopyrimidine: A New Scaffold for Dual-Target Small Molecules for Alzheimer's Disease Therapy
2020; 25 (14)
Alzheimer's disease (AD) is multifactorial disease characterized by the accumulation of abnormal extracellular deposits of amyloid-beta (Aβ) peptide, and intracellular neurofibrillary tangles (NFTs), along with dramatic neuronal death and decreased levels of choline acetyltransferase. Given the limited therapeutic success of available drugs, it is urgent to explore all the opportunities available to combat this illness. Among them, the discovery of new heterocyclic scaffolds binding different receptors involved in AD should offer structural diversity and new therapeutic solutions. In this context, this work describes new triazolopyridopyrimidine easily prepared in good yields showing anticholinesterase inhibition and strong antioxidant power, particularly the most balanced: 6-amino-5-(4-methoxyphenyl)-2-phenyl-[1,2,4]triazolo[1',5':1,6] pyrido[2,3-d]pyrimidine-4-carbonitrile(3c) with IC50 equal to 1.32 μM against AChE and oxygen radical absorbance capacity (ORAC) value equal to 4.01 Trolox equivalents (TE); thus representing a new and very promising hit-triazolopyridopyrimidine for AD therapy.
View details for DOI 10.3390/molecules25143190
View details for Web of Science ID 000554788700001
View details for PubMedID 32668671
View details for PubMedCentralID PMC7397274
Design, Synthesis and Biological Evaluation of New Antioxidant and Neuroprotective Multitarget Directed Ligands Able to Block Calcium Channels
2020; 25 (6)
We report herein the design, synthesis and biological evaluation of new antioxidant and neuroprotective multitarget directed ligands (MTDLs) able to block Ca2+ channels. New dialkyl 2,6-dimethyl-4-(4-(prop-2-yn-1-yloxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate MTDLs 3a-t, resulting from the juxtaposition of nimodipine, a Ca2+ channel antagonist, and rasagiline, a known MAO inhibitor, have been obtained from appropriate and commercially available precursors using a Hantzsch reaction. Pertinent biological analysis has prompted us to identify the MTDL 3,5-dimethyl-2,6-dimethyl-4-[4-(prop-2-yn-1-yloxy)phenyl]-1,4-dihydro- pyridine- 3,5-dicarboxylate (3a), as an attractive antioxidant (1.75 TE), Ca2+ channel antagonist (46.95% at 10 μM), showing significant neuroprotection (38%) against H2O2 at 10 μM, being considered thus a hit-compound for further investigation in our search for anti-Alzheimer's disease agents.
View details for DOI 10.3390/molecules25061329
View details for Web of Science ID 000530248700072
View details for PubMedID 32183349
View details for PubMedCentralID PMC7144121
Synthesis of new ferulic/lipoic/comenic acid-melatonin hybrids as antioxidants and Nrf2 activators via Ugi reaction
FUTURE MEDICINAL CHEMISTRY
2019; 11 (24): 3097–3108
Aim: Oxidative stress has been implicated in the pathogenesis of many neurodegenerative diseases, and particularly in Alzheimer's disease. Results: This work describes the Ugi multicomponent synthesis, antioxidant power and Nrf2 pathway induction in antioxidant response element cells of (E)-N-(2-((2-(1H-indol-3-yl)ethyl)amino)-2-oxoethyl)-N-(2-(5-(benzyloxy)-1H-indol-3-yl)ethyl)-3-(4-hydroxy-3-methoxyphenyl)acryl amides 8a-d, N-(2-((2-(1H-indol-3-yl)ethyl)amino)-2-oxoethyl)-N-(2-(5-(benzyloxy)-1H-indol-3-yl)ethyl)-5-(1,2-dithiolan-3-yl)pentanamides 8e-h and N-(2-((2-(1H-indol-3-yl)ethyl)amino)-2-oxoethyl)-N-(2-(5-(benzyloxy)-1H-indol-3-yl)ethyl)-5-hydroxy-4-oxo-4H-pyran-2-carboxamides 8i,j. Conclusion: We have identified compounds 8e and 8g, showing a potent antioxidant capacity, a remarkable neuroprotective effect against the cell death induced by H2O2 in SH-SY5Y cells, and a performing activation of the Nrf2 signaling pathway, as very interesting new antioxidant agents for pathologies that curse with oxidative stress.
View details for DOI 10.4155/fmc-2019-0191
View details for Web of Science ID 000502771800002
View details for PubMedID 31838896
Synthesis, antioxidant and A beta anti-aggregation properties of new ferulic, caffeic and lipoic acid derivatives obtained by the Ugi four-component reaction
2019; 85: 221–28
We report herein the synthesis antioxidant and Aβ anti-aggregation capacity of (E)-N-benzyl-N-[2-(benzylamino)-2-oxoethyl]-3-(aryl)acrylamides and related (R)-N-benzyl-N-(2-(benzylamino)-2-oxoethyl)-5-(1,2-dithiolan-3-yl)pentanamides 1-12. These compounds have been obtained, via Ugi four-component reaction, from modest to good yields. Their antioxidant analysis, using the DPPH and ORAC assays, allowed us to identify compounds 8 and 9, as potent antioxidant agents, showing also strong Aβ1-40 self-aggregation inhibition, two biological properties of interest in pathologies linked to the oxidative stress, such as Alzheimer's disease.
View details for DOI 10.1016/j.bioorg.2018.12.029
View details for Web of Science ID 000462472500022
View details for PubMedID 30640071
Donepezil plus chromone plus melatonin hybrids as promising agents for Alzheimer's disease therapy
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
2019; 34 (1): 479–89
We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC50 = 11.90 ± 0.05 nM), moderate hAChE (IC50 = 1.73 ± 0.34 μM), hMAO A (IC50 = 2.78 ± 0.12 μM), and MAO B (IC50 = 21.29 ± 3.85 μM) inhibition, while keeping a strong antioxidant power (3.04 TE, ORAC test). Consequently, the results reported here support the development of new multitarget Donepezil + Chromone + Melatonin hybrids, such as compound 14n, as a potential drug for AD patients cure.
View details for DOI 10.1080/14756366.2018.1545766
View details for Web of Science ID 000457532600001
View details for PubMedID 30712420
View details for PubMedCentralID PMC6366423