Antihistamines H3R/H4R as procognitive agents: a multitarget approach

• Grant number: 16/25028-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2017
• End date: June 30, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: João Paulo dos Santos Fernandes
• Grantee: João Paulo dos Santos Fernandes
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• City of the host institution: Diadema
• Associated researchers: Claudio Miguel da Costa Neto

Abstract

Aging is generally associated with a certain cognitive decline. Although individual differences exist, the mechanisms underlying learning and memory processes are complex and commonly explored in the search for targets to drug therapy. Certain pathological conditions, such as Alzehimer's and Parkinson's diseases, vascular dementia and mood and affective disorders affect cognition. Considering this, the search for new molecules capable to improve the cognitive processes, sometimes known as nootropic agents, is constantly on the focus of pharmaceutical companies as well as in academic research. The role of histaminergic, cholinergic and dopaminergic systems, in addition to increased cerebral blood flow, is widely known and can be considered among the main targets for new drugs. Moreover, it is proposed these conditions are better treated through a multitarget approach, i.e. by affecting more than one target in the same time. With this regards, the present project aims to synthesize and evaluate the activity of a set of dihydrobenzofuranyl-piperazines in in vitro assays in vessels and in the respective receptors, and to the more promising compounds, in cognition models in vivo. The compounds will be prepared mainly by methodologies developed in our group, which usually give good yields. It is expected the set designed can bring some information of SAR that can be valuable to optimize the activity of new compounds in each target, as well as in a multitarget approach. (AU)

Scientific publications

(21)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

FRANCHIN, TAISA BUSARANHO; ULIAN SILVA, BRUNA CRISTINA; DEGRANDIS, RONE APARECIDO; CORREA, MICHELLE FIDELIS; SIMOES DE QUEIROZ ARANHA, CECILIA MARIA; FERNANDES, JOAO PAULO S.; CAMPOS, MICHEL LEANDRO; PECCININI, ROSANGELA GONCALVES. Assessment of the Physicochemical Properties and Stability for Pharmacokinetic Prediction of Pyrazinoic Acid Derivatives. CURRENT DRUG METABOLISM, v. 21, n. 9, p. 714-721, 2020. (16/23139-2, 16/25028-3, 16/23229-1)

VASCONCELOS, CAMILLA I.; VARELA, MARINA T.; TORRECILHAS, ANA C.; FERNANDES, JOAO P. S.. Pyrazinoates as antiparasitic agents against Trypanosoma cruzi. ARCHIV DER PHARMAZIE, v. 351, n. 11, NOV 2018. (16/01917-3, 18/03918-2, 16/25028-3)

OLIVEIRA, LIDIANE; FERRARINI, MARCIO; DOS SANTOS, ALEXANDRE PAES; VARELA, MARINA THEMOTEO; SANTOS CORREA, ISABELA TERESA; TEMPONE, ANDRE GUSTAVO; MELHEM, MARCIA S. C.; VALLIM, MARCELO A.; FERNANDES, JOAO PAULO S.; PASCON, RENATA C.. Coumaric acid analogues inhibit growth and melanin biosynthesis in Cryptococcus neoformans and potentialize amphotericin B antifungal activity. European Journal of Pharmaceutical Sciences, v. 153, OCT 1 2020. (18/10279-6, 18/03918-2, 15/04400-9, 16/25028-3, 16/14542-8)

MORAIS, THIAGO R.; ALVES CONSERVA, GEANNE A.; VARELA, MARINA T.; COSTA-SILVA, THAIS A.; THEVENARD, FERNANDA; PONCI, VITOR; FORTUNA, ANA; FALCAO, AMILCAR C.; TEMPONE, ANDRE G.; FERNANDES, JOAO PAULO S.; et al. Improving the drug-likeness of inspiring natural products - evaluation of the antiparasitic activity against Trypanosoma cruzi through semi-synthetic and simplified analogues of licarin A. SCIENTIFIC REPORTS, v. 10, n. 1, MAR 25 2020. (16/20633-6, 16/25028-3, 18/10279-6, 18/07885-1)

GINOZA, MILTON; FERNANDES, GUSTAVO A. B.; CORREA, MICHELLE F.; FERNANDES, JOAO PAULO S.. Novel potent vasodilating agents: Evaluation of the activity and potency of LINS01005 and derivatives in rat aorta. European Journal of Pharmaceutical Sciences, v. 143, FEB 15 2020. (17/05441-6, 16/23139-2, 16/25028-3)

SOLIANI, ANDRESSA; KUBOTA, SILVIA MEGUMI; CORREA, MICHELLE FIDELIS; CERUTTI, SUZETE MARIA; FERNANDES, JOAO PAULO S.. Differential contribution of H3R antagonism by LINS01 compounds on memory, anxiety-like behaviour and spontaneous locomotor activity in healthy rats. Behavioural Brain Research, v. 377, JAN 13 2020. (16/18039-9, 16/25028-3, 16/23139-2)

VARELA, MARINA T.; COSTA-SILVA, THAIS A.; LAGO, JOAO HENRIQUE G.; TEMPONE, ANDRE G.; FERNANDES, JOAO PAULO S.. Evaluation of the antitrypanosoma activity and SAR study of novel LINS03 derivatives. BIOORGANIC CHEMISTRY, v. 89, AUG 2019. (18/03918-2, 16/25028-3, 18/07885-1, 15/23403-9)

CORRE, MICHELLE F.; BALICO-SILVA, ANDRE L.; KISS, DORA J.; FERNANDES, GUSTAVO A. B.; MARASCHIN, JHONATAN C.; PARREIRAS-E-SILVA, LUCAS T.; VARELA, MARINA T.; SIMOES, SARAH C.; BOUVIER, MICHEL; KESERU, GYORGY M.; et al. Novel potent (dihydro)benzofuranyl piperazines as human histamine receptor ligands - Functional characterization and modeling studies on H-3 and H(4 )receptors. Bioorganic & Medicinal Chemistry, v. 30, JAN 15 2021. (16/24120-3, 17/05441-6, 12/20148-0, 16/25028-3, 18/03918-2, 18/00153-5, 16/08920-0, 16/23139-2)

WALLER, STEFANIE BRESSAN; CLEFF, MARLETE BRUM; RIPOLL, MARCIA KUTSCHER; ARAUJO MEIRELES, MARIO CARLOS; FERRARINI, MARCIO; VARELA, MARINA THEMOTEO; FERNANDES, JOAO PAULO S.. ioisosteric modification on benzylidene-carbonyl compounds improved the drug-likeness and maintained the antifungal activity against Sporothrix brasiliensi. CHEMICAL BIOLOGY & DRUG DESIGN, v. 99, n. 3, DEC 2021. (18/03918-2, 19/24028-8, 16/25028-3)

CORREA, MICHELLE F.; BARBOSA, ALEFE J. R.; TEIXEIRA, LARISSA B.; DUARTE, DIEGO A.; SIMOES, SARAH C.; PARREIRAS-E-SILVA, LUCAS T.; BALBINO, ALEKSANDRO M.; LANDGRAF, RICHARDT G.; BOUVIER, MICHEL; COSTA-NETO, CLAUDIO M.; et al. Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines: Novel Antagonists for the Histamine H-3 and H-4 Receptors with Anti-inflammatory Potential. FRONTIERS IN PHARMACOLOGY, v. 8, NOV 14 2017. (12/20148-0, 17/02042-3, 16/23139-2, 16/25028-3, 13/20479-9)

CORREA, MICHELLE FIDELIS; DOS SANTOS FERNANDES, JOAO PAULO. Targeting the Histamine H-4 Receptor: Future Drugs for Inflammatory Diseases. CURRENT ORGANIC CHEMISTRY, v. 22, n. 17, p. 1663-1672, 2018. (16/25028-3)

CORREA, MICHELLE F.; REINER, DAVID; FERNANDES, GUSTAVO A. B.; VARELA, MARINA T.; ARANHA, CECILIA M. S. Q.; STARK, HOLGER; FERNANDES, JOAO PAULO S.. Profiling of LINS01 compounds at human dopamine D-2 and D-3 receptors. JOURNAL OF CHEMICAL SCIENCES, v. 132, n. 1, DEC 2019. (17/05441-6, 18/03918-2, 18/04488-1, 16/25028-3)

CORREA, MICHELLE FIDELIS; RAMOS BARBOSA, ALEFE JHONATAS; BORGES FERNANDES, GUSTAVO ARIEL; BAKER, JILLIAN G.; DOS SANTOS FERNANDES, JOAO PAULO. Pharmacological and SAR analysis of the LINS01 compounds at the human histamine H-1, H-2, and H-3 receptors. CHEMICAL BIOLOGY & DRUG DESIGN, v. 93, n. 1, p. 89-95, JAN 2019. (16/25028-3, 17/05441-6, 16/23139-2)

VARELA, MARINA THEMOTEO; FERRARINI, MARCIO; MERCALDI, VITORIA GALLO; SUFI, BIANCA DA SILVA; PADOVANI, GIOVANA; SBRUGNERA NAZATO, LUCAS IDACIR; FERNANDES, JOAO PAULO S.. Coumaric acid derivatives as tyrosinase inhibitors: Efficacy studies through in silico, in vitro and ex vivo approaches. BIOORGANIC CHEMISTRY, v. 103, p. 11-pg., 2020-10-01. (16/25028-3, 18/03918-2)

CORREA, MICHELLE F.; REINER, DAVID; FERNANDES, GUSTAVO A. B.; VARELA, MARINA T.; ARANHA, CECILIA M. S. Q.; STARK, HOLGER; FERNANDES, JOAO PAULO S.. Profiling of LINS01 compounds at human dopamine D₂ and D₃ receptors. JOURNAL OF CHEMICAL SCIENCES, v. 132, n. 1, p. 6-pg., 2019-12-01. (18/03918-2, 16/25028-3, 18/04488-1, 17/05441-6)

MORAIS, THIAGO R.; ALVES CONSERVA, GEANNE A.; VARELA, MARINA T.; COSTA-SILVA, THAIS A.; THEVENARD, FERNANDA; PONCI, VITOR; FORTUNA, ANA; FALCAO, AMILCAR C.; TEMPONE, ANDRE G.; FERNANDES, JOAO PAULO S.; et al. Improving the drug-likeness of inspiring natural products - evaluation of the antiparasitic activity against Trypanosoma cruzi through semi-synthetic and simplified analogues of licarin A. SCIENTIFIC REPORTS, v. 10, n. 1, p. 14-pg., 2020-03-25. (18/07885-1, 16/20633-6, 16/25028-3, 18/10279-6)

BALBINO, A. M.; LIMA, L. J. S.; FERNANDES, G. A. B.; CORREA, M. F.; LANDGRAF, M. A. V.; FERNANDES, J. P. S.; LANDGRAF, R. G.. MODULATORY EFFECTS OF HISTAMINE H3R/H4R ANTAGONISTS LINS01005 AND LINS01007 ON THE INFLAMMATORY RESPONSE IN MURINE ASTHMA MODEL. Inflammation Research, v. 68, p. 1-pg., 2019-07-01. (12/51104-8, 17/02042-3, 16/23139-2, 16/25028-3, 17/05441-6)

CORREA, M. F.; SILVA, A. B.; PENOMIAN, L.; SIMOES, S. C.; FERNANDES, G. A. B.; ARANHA, C. M. S. Q.; VARELA, M. T.; COSTA-NETO, C. M.; FERNANDES, J. P. S.. EVALUATION AND SAR STUDY OF NOVEL SUBSTITUTED (DIHYDRO)BENZOFURANYL-PIPERAZINES AS HISTAMINE H3R AND H4R LIGANDS. Inflammation Research, v. 68, p. 1-pg., 2019-07-01. (18/04488-1, 18/03918-2, 16/23139-2, 16/25028-3, 17/05441-6)

VARELA, MARINA T.; ROMANELI, MAIARA M.; LIMA, MARTA L.; BORBOREMA, SAMANTA E. T.; TEMPONE, ANDRE G.; FERNANDES, JOAO P. S.. Antiparasitic activity of new gibbilimbol analogues and SAR analysis through efficiency and statistical methods. European Journal of Pharmaceutical Sciences, v. 122, p. 31-41, SEP 15 2018. (16/25028-3, 15/23403-9, 16/00195-4)

WALLER, STEFANIE BRESSAN; CLEFF, MARLETE BRUM; RIPOLL, MARCIA KUTSCHER; ARAUJO MEIRELES, MARIO CARLOS; VARELA, MARINA THEMOTEO; FERNANDES, JOAO PAULO DOS S.. Benzylidene-carbonyl compounds are active against itraconazole-susceptible and itraconazole-resistantSporothrix brasiliensis. Folia Microbiologica, v. 65, n. 6, AUG 2020. (16/25028-3, 18/03918-2)

VARELA, MARINA THEMOTEO; FERNANDES, JOAO PAULO S.. Natural Products: Key Prototypes to Drug Discovery against Neglected Diseases Caused by Trypanosomatids. Current Medicinal Chemistry, v. 27, n. 13, p. 2133-2146, 2020. (16/25028-3, 16/00195-4)