Planning and synthesis of inhibitors based on biological targets: the case of neglected kinases

• Grant number: 19/13104-5
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2019
• End date: September 30, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Ronaldo Aloise Pilli
• Grantee: Ronaldo Aloise Pilli
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Rafael Lemos Miguez Couñago

Abstract

This research proposal deals with the synthesis of heterocyclic compounds to be investigated as chemical probes and inhibitors of the neglected kinases LOK/STK10, VRK1 and VRK2 as well as the synthesis of brazilin and its analogues in order to probe their cytotoxic activities against cancer cell lines both in the non-encapsulated and associated with AcDex nanoparticles. The structures of the inhibitors of the LOK/STK10, VRK1 and VRK2 kinases to be prepared will be defined based on docking studies and DRX data of co-crystals of these enzymes and structurally related ligands. (AU)

Scientific publications

(12)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GRIGOLO, THIAGO A.; BRAGA, CAROLYNE B.; ORNELAS, CATIA; RUSSOWSKY, DENNIS; FERREIRA-SILVA, GUILHERME A.; IONTA, MARISA; PILLI, RONALDO A.. Hybrids of 4-hydroxy derivatives of goniothalamin and piplartine bearing a diester or a 1,2,3-triazole linker as antiproliferative agents. BIOORGANIC CHEMISTRY, v. 116, NOV 2021. (17/06146-8, 18/02093-0, 13/07607-8, 19/13104-5)

DE TOLEDO, IAN; GRIGOLO, THIAGO; BENNETT, JAMES M.; ELKINS, JONATHAN M.; PILLI, RONALDO A.. Modular Synthesis of Di- and Trisubstituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors. Journal of Organic Chemistry, v. 84, n. 21, p. 14187-14201, NOV 1 2019. (13/07607-8, 19/13104-5)

BERNARDI ROSSO, GIOVANNI; MATOS PAZ, BRUNO; ALOISE PILLI, RONALDO. Formal Syntheses of (+/-)-Tuberostemospiroline and (+/-)-Stemona-lactam R and Total Synthesis of (+/-)-Stemoamide. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. 2022, n. 28, p. 6-pg., 2022-07-27. (19/13104-5, 18/05742-9)

DELLA-FELICE, FRANCO; BARTOLOMEU, ALOISIO DE ANDRADE; PILLI, RONALDO ALOISE. The phosphate ester group in secondary metabolites. NATURAL PRODUCT REPORTS, v. 39, n. 5, p. 42-pg., 2022-04-14. (16/12541-4, 14/25474-8, 19/13104-5, 13/07607-8, 20/07991-6)

REGUEIRA, JULIANA L. L. F.; SILVA JR, LUIZ F.; PILLI, RONALDO A.. Total Synthesis of (+)-Raputindole A: An Iridium-Catalyzed Cyclization Approach. ORGANIC LETTERS, v. 22, n. 16, p. 6262-6266, AUG 21 2020. (19/13104-5)

DE SOUZA, VANESSA P.; SANTOS, FABIANO S.; RODEMBUSCH, FABIANO S.; BRAGA, CAROLYNE B.; ORNELAS, CATIA; PILLI, RONALDO A.; RUSSOWSKY, DENNIS. Hybrid 3,4-dihydropyrimidin-2-(thi)ones as dual-functional bioactive molecules: fluorescent probes and cytotoxic agents to cancer cells. NEW JOURNAL OF CHEMISTRY, v. 44, n. 29, p. 12440-12451, AUG 7 2020. (17/06146-8, 19/13104-5, 18/02093-0)

SILVA, MARCELA C. R.; VILELA, ADRIANA F. L.; CARDOSO, CARMEN L. L.; PILLI, RONALDO A. A.. Synthesis and Anticholinesterase Evaluation of Cassine, Spectaline and Analogues. SCIENTIA PHARMACEUTICA, v. 90, n. 4, p. 21-pg., 2022-01-01. (14/50249-8, 19/13104-5, 16/02873-0, 16/12541-4)

MEIRELLES, MATHEUS A.; DE TOLEDO, IAN; THUROW, SAMUEL; BARREIRO, GABRIELA; COUNAGO, RAFAEL M.; PILLI, RONALDO A.. Functionalization of 2,4-Dichloropyrimidines by 2,2,6,6-Tetramethylpiperidyl Zinc Base Enables Modular Synthesis of Antimalarial Diaminopyrimidine P218 and Analogues. Journal of Organic Chemistry, v. 88, n. 13, p. 13-pg., 2023-06-08. (14/50897-0, 19/25008-0, 19/20735-1, 19/13104-5, 13/50724-5)

BRAGA, CAROLYNE B.; KIDO, LARISSA A.; LIMA, ELLEN N.; LAMAS, CELINA A.; CAGNON, VALERIA H. A.; ORNELAS, CATIA; PILLI, RONALDO A.. Enhancing the Anticancer Activity and Selectivity of Goniothalamin Using pH-Sensitive Acetalated Dextran (Ac-Dex) Nanoparticles: A Promising Platform for Delivery of Natural Compounds. ACS BIOMATERIALS SCIENCE & ENGINEERING, v. 6, n. 5, SI, p. 2929-2942, MAY 2020. (18/02093-0, 17/06146-8, 19/13104-5, 13/07607-8)

LUSSARI, NATALIA; KHAN, AJMIR; PILLI, RONALDO A.; DOS SANTOS, ALCINDO A.; SILVA, LUIZ F., JR.; BRAGA, ATAUALPA A. C.. A DFT study on the formation of heterocycles via iodine(iii)-promoted ring expansion reactions. NEW JOURNAL OF CHEMISTRY, v. 46, n. 43, p. 11-pg., 2022-10-12. (19/13104-5, 14/25770-6, 15/01491-3)

BRAGA, CAROLYNE B.; KIDO, LARISSA A.; LIMA, ELLEN N.; LAMAS, CELINA A.; CAGNON, VALERIA H. A.; ORNELAS, CATIA; PILLI, RONALDO A.. Enhancing the Anticancer Activity and Selectivity of Goniothalamin Using pH-Sensitive Acetalated Dextran (Ac-Dex) Nanoparticles: A Promising Platform for Delivery of Natural Compounds. ACS BIOMATERIALS SCIENCE & ENGINEERING, v. 6, n. 5, p. 14-pg., 2020-05-01. (18/02093-0, 17/06146-8, 13/07607-8, 19/13104-5)

BRAGA, CAROLYNE B.; PILLI, RONALDO A.; ORNELAS, CATIA; WECK, MARCUS. ear-Infrared Fluorescent Micelles from Poly(norbornene) Brush Triblock Copolymers for Nanotheranostic. Biomacromolecules, v. 22, n. 12, p. 5290-5306, DEC 13 2021. (13/07607-8, 19/13104-5, 14/50906-9, 18/24020-4, 17/06146-8)