Modelado computacional para la obtención de moléculas bioactivas

Formulación de estudios de relación estructura-actividad para la predicción de actividad biológica y el diseño de fármacos.

Proyectos

• Puente UV «Formulacion de modelos de relacion estructura actividad cuantitativos QSAR» (2021)
• FONDECYT Regular 1201395 «Drimanic sesquiterpens and lichen metabolites as building block for the synthesis of new sesquiterpene-orcinol derivatives, as potential topoisomerase I/ II, and or PDK1 kinase inhibitors» (2020-2023). Convestigador
• FONDECYT Regular 1191330 «Synthesis of new brassinosteroid analogs with structural changes in the side chain. Evaluation of growth promoting effect and in silico structure-activity studies» (2019-2023). Coinvestigador
• FONDECYT Regular 1150121 «Synthesis, binding mode prediction, biological evaluation and SAR analysis of benzoimidazole-based modulators of the endocannabinoid system» (2015-2019). Coinvestigador
• FONDECYT de Iniciación en Investigación 11130701 «Rational design, synthesis, biological
  evaluation and quantitative structureactivity relationships of novel ß3-AR ligands» (2013-2017). Investigador responsable

Publicaciones

• Lorca M, et al. Cancer and brassinosteroids: Mechanisms of action, SAR and future perspectives. Steroids 2023, 190:109153. 10.1016/j.steroids.2022.109153.
• Cabezas D, et al. In silico approaches to develop new phenyl-pyrimidines as glycogen synthase kinase 3 (GSK-3) inhibitors with halogen-bonding capabilities: 3D-QSAR CoMFA/CoMSIA, molecular docking and molecular dynamics studies. Journal of Biomolecular Structure and Dynamics 2023, 10.1080/07391102.2023.2172457
• Lorca M, et al. Design of benzimidazoles, benzoxazoles, benzothiazoles and thiazolopyridines as leukotriene A4 hydrolase inhibitors through 3D-QSAR, docking and molecular dynamics. Journal of the Serbian Chemical Society 2023, 88(1), 25-39 10.2298/JSC220427068L
• Bertrand J, et al. Design, Synthesis, In Silico Studies and Inhibitory Activity towards Bcr-Abl, BTK and FLT3-ITD of New 2,6,9-Trisubstituted Purine Derivatives as Potential Agents for the Treatment of Leukaemia. Pharmaceutics 2022, 14(6):1294. 10.3390/pharmaceutics14061294
• Erol M, et al. Synthesis, molecular modeling, 3D-QSAR and biological evaluation studies of new benzimidazole derivatives as potential MAO-A and MAO-B inhibitors. Journal of Molecular Structure 2022, 1265:133444 10.1016/j.molstruc.2022.133444
• Mellado M, et al. QSAR-driven synthesis of antiproliferative chalcones against SH-SY5Y cancer cells: Design, biological evaluation, and redesign. Arch. Pharm. 2022, 355:e2200042. 10.1002/ardp.202200042
• Çevik UA, et al. Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor. ACS Omega 2022, 7, 18:16152–16163. 10.1021/acsomega.2c01497 
• Mellado M, et al. CoumarinResveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin. Molecules 2022, 27(3):928 ;
  10.3390/molecules27030928
• Mellado M, et al. Combined 3D-QSAR and docking analysis for the design and synthesis of chalcones as potent and selective monoamine oxidase B inhibitors. Bioorganic Chemistry 2021, 108,104689. 10.1016/j.bioorg.2021.104689
• Arrieta-Rodríguez L, et al. Novel N-Arylsulfonylindoles Targeted as Ligands of the 5-HT₆ Receptor. Insights on the Influence of C-5 Substitution on Ligand Affinity. Pharmaceuticals 2021, 14(6):528. 10.3390/ph14060528
• Cerda-Cavieres C, et al. Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands. Molecules 2020, 25(20):4614. 10.3390/molecules25204614
• Rodriguez-Lavados J, et al. Synthesis, in vitro evaluation and molecular docking of a new class of indolylpropyl benzamidopiperazines as dual AChE and SERT ligands for Alzheimer’s disease. European Journal of Medicinal Chemistry 2020, 198, 112368 10.1016/j.ejmech.2020.112368
• Mella-Raipán J, et al. DARK Classics in Chemical Neuroscience: Heroin and Desomorphine. ACS Chem Neurosci. 2020,11(23):3905-3927. 10.1021/acschemneuro.0c00262. 
• Mellado M, et al. 3-Arylcoumarins as highly potent and selective monoamine oxidase B inhibitors: Which chemical features matter? Bioorganic Chemistry 2020, 101:103964 10.1016/j.bioorg.2020.103964
• Salas CO, et al. Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays. International Journal of Molecular Sciences 2020,21(1):161 10.3390/ijms21010161
• Bertrand J, et al. New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia. Bioorganic Chemistry 2020, 94:103361.  10.1016/j.bioorg.2019.103361
• Mellado M, et al. Design, synthesis, antifungal activity, and structure-activity relationship studies of chalcones and hybrid dihydrochromane-chalcones.  Molecular Diversity 2020, 24:603-615. 10.1007/s11030-019-09967-y
• Lorca M, et al. Three-Dimensional Quantitative Structure-Activity Relationships (3D-QSAR) on a Series of Piperazine-Carboxamides Fatty Acid Amide Hydrolase (FAAH) Inhibitors as a Useful Tool for the Design of New Cannabinoid Ligands. International Journal of Molecular Sciences 2019, 20(10):2510 10.3390/ijms20102510
• Suarez-Rozas C, et al. Antiproliferative and proapoptotic activities of aza-annulated naphthoquinone analogs. Toxicology in Vitro 2019, 54, 375-390 10.1016/j.tiv.2018.10.014
• Mellado M, et al. Design, synthesis, antifungal activity, and structure–activity relationship studies of chalcones and hybrid dihydrochromane–chalcones. Molecular Diversity 2019 10.1007/s11030-019-09967-y 
• González-Gutiérrez JP, et al. Synthesis of novel nicotinic ligands with multimodal action: Targeting Acetylcholine α4β2, Dopamine and Serotonin Transporters. Molecules 2019, 24(20), 3808 10.3390/molecules24203808
• Espinosa-Bustos C, et al. State of the art of Smo antagonists for cancer therapy: advances in the target receptor and new ligand structures. Future Medicinal Chemistry 2019, 11, 615-636. 10.4155/fmc-2018-0497
• Cañete-Molina Á, et al. Design, synthesis, cytotoxicity and 3D-QSAR analysis of new 3,6-disubstituted-1,2,4,5-tetrazine derivatives as potential antitumor agents. Arabian Journal of Chemistry 2019, 12:1092-1107 10.1016/j.arabjc.2017.04.002
• Lorca M, et al. Structure-Activity Relationships Based on 3D-QSAR CoMFA/CoMSIA and Design of Aryloxypropanol-Amine Agonists with Selectivity for the Human β3-Adrenergic Receptor and Anti-Obesity and Anti-Diabetic Profiles. Molecules 2018, 23(5):1191. 10.3390/molecules23051191
• Mellado M, etl al.  Synthesis of chalcones with antiproliferative activity on the SH-SY5Y neuroblastoma cell line: Quantitative Structure–Activity. Medicinal Chemistry Research 2018, 27, 2414–2425 10.1007/s00044-018-2245-2
• Mellado M, et al. Hansch’s analysis application to chalcone synthesis by Claisen–Schmidt reaction based in DFT methodology. Chemical Papers 2018, 72, 703-709 10.1007/s11696-017-0316-3
• López-Lira C, et al. Combined molecular modeling and 3D-QSAR study for understanding the inhibition of NQO1 by heterocyclic quinone derivatives. Chemical Biology and Drug Design 2018, 91:29-38. 10.1111/cbdd.13051
• Campanini-Salinas J, et al. Novel classes of antibacterial drugs in clinical development, a hope in post antibiotic era. Current Topics Medicinal Chemistry 2018, 18(14):1188-1202 10.2174/1568026618666180816162846
• Campanini-Salinas J, et al. A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections. Molecules 2018, 23(7):1776 10.3390/molecules23071776
• Ferrer-Pertuz K, et al. Insights into the Structural Requirements of Potent Brassinosteroids as Vegetable Growth Promoters Using Second-Internode Elongation as Biological Activity: CoMFA and CoMSIA Studies. International Journal of Molecular Sciences 2017;18(12):2734. 10.3390/ijms18122734
• Apablaza G, et al. 2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-Phenylethan-1-ol with Human β3-Adrenergic Activity. Molecules 2017, 22(3), 404. 10.3390/molecules22030404
• Romero-Parra J, et al. Combined CoMFA and CoMSIA 3D-QSAR study of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor. European Journal of Medicinal Chemistry 2017, 101, 1-10 10.1016/j.ejps.2017.01.037
• Mella J, et al. Structure-Activity Relationships Studies on Weakly Basic N-Arylsulfonylindoles with an Antagonistic Profile in the 5-HT6 Receptor. Journal of Molecular Structure 2017, 1139, 362-370 10.1016/j.molstruc.2017.03.067
• Vera G, et al. Extended NArylsulfonylindoles as 5-HT(6) Receptor Antagonists: Design, Synthesis & Biological Evaluation. Molecules 2016, 21(8):1070 10.3390/molecules21081070
• Romero-Parra J, et al. Synthesis, binding assays, cytotoxic activity and docking studies of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor. European Journal of Medicinal Chemistry 2016, 124:17-35. 10.1016/j.ejmech.2016.08.005
• Espinosa-Bustos C, et al. Design, synthesis, biological evaluation and binding mode  modeling of benzimidazole derivatives targeting the cannabinoid receptor type 1. Arch Pharm 2015, 348:81-8. 10.1002/ardp.201400201
• Andrades J, et al. A combined CoMFA and CoMSIA 3D-QSAR study of benzamide type antibacterial inhibitors of the FtsZ protein in drug-resistant Staphylococcus aureus. SAR and QSAR Environmental Research 2015, 26:925-42 10.1080/1062936X.2015.1095798
• Mella-Raipan J, et al. 3DQSAR/CoMFA-based structure-affinity/selectivity relationships of aminoalkylindoles in the cannabinoid CB1 and CB2 receptors. Molecules 2014, 19:2842-61
  10.3390/molecules19032842

Presentaciones en congresos

• IX Congreso iberoamericano de ciencias farmacéuticas COIFFA. Póster «Obtención de un nuevo farmacóforo de tipo benzimidazol como inhibidor de la enzima Bcr-Abl nativa y mutada mediante Diseño de novo, con potencial aplicación anti leucémica». Guatemala, Noviembre 2021
• VII Congreso iberoamericano de química de productos naturales. Póster «Diseño mediante docking y síntesis de derivados sesquiterpendrimanos para el tratamiento de neoplasias». Punta Arenas, Chile. Noviembre 2021
• 26th YRFM Young Research Fellows Meeting. Póster “N-arylsulfonylindole and Narylsulfonylindazole as potential anti-obesity drugs: Design, synthesis, biological assessment and structure-activity studies”. París, Francia. Febrero, 2019
• III International Symposium on Integrative Bioinformatics. Póster «Combined CoMFA,
  CoMSIA, molecular docking and molecular dynamics studies of histone deacetylase I inhibitors» Pucón, Chile. Diciembre 2019
• XXXIII Jornadas Chilenas de Química. Póster «Diseño racional, sintesis y evaluacion
  farmacologica de nuevos derivados heterociclicos del tipo benzoimidazoletanolamina con potencial acvtividad ß3-adrenérgica» San Luis, Argentina. Noviembre 2017
• XXXII Congreso Latinoamericano de Química (CLAQ). Pósters «Lead optimization of pyrimido[4,5-c]isoquinolines with antibacterial activity based in free-wilson 2d-qsar analysis.» y «Develop of new ubiquinone analogs as antibacterial agents from 3d-qsar/comfa models». Concepción, Chile. 2016

Identificador ORCID 0000-0002-2434-8461