New antineoplastic agents: synthesis, molecular docking and antitumoral activity of capsaicinoids analogues

• Grant number: 17/00689-0
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2018 - February 29, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Roberto Parise Filho
• Grantee: Roberto Parise Filho
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ricardo Alexandre de Azevedo

Abstract

Cancer is one of the leading causes of death worldwide. Recent studies reported that capsaicinoids, substances found in several species of peppers, have shown interesting antitumor activity by inducing selective apoptosis in tumors via TRPV receptors. Thus, the use of these compounds as structural models for the synthesis of analogues with potentially higher activity and lower toxicity is a subject of great interest. Therefore, this project aims to synthesize capsaicinoid analogs designed by molecular modification, to evaluate their antitumor potential and to investigate the modus interandi with TRPV6 type receptors. The analogues will be synthesized using methods such as condensation, triazoles formation, acylation, sulfonylation and thioacylation and subsequently they will be evaluated for cytotoxic capacity in tumorigenic and non-tumorigenic cells. Regarding the most promising analogues, pro-apoptotic properties, cell cycle arrest, and other biochemical pathways could be performed in order to elucidate the mode of action of those compounds. Molecular docking simulations will be performed for the most promising analogues in order to elucidate the modus interandi aiming the design of new optimized scaffolds, which could have enhanced affinities for the target biological target (TRPV6). The results will contribute to the knowledge of the molecular mechanisms involved in the antitumor response of capsaicinoid compounds and analogues, as well as to the discovery of potential substances that might be an alternative in the treatment of cancer. (AU)

Scientific publications

(10)

(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)

TAVARES, MAURICIO TEMOTHEO; DE ALMEIDA, LARISSA COSTA; KRONENBERGER, THALES; FERREIRA, GLAUCIO MONTEIRO; DE DIVITIIS, THAINA FUJII; TOLEDO, MONICA FRANCO ZANNINI JUNQUEIRA; HASSIMOTTO, NEUZA MARIKO AYMOTO; MACHADO-NETO, JOAO AGOSTINHO; COSTA-LOTUFO, LETICIA VERAS; PARISE-FILHO, ROBERTO. Structure-activity relationship and mechanistic studies for a series of cinnamyl hydroxamate histone deacetylase inhibitors. Bioorganic & Medicinal Chemistry, v. 35, APR 1 2021. (15/17177-6, 13/19311-6, 17/00689-0)

KRONENBERGER, THALES; FERREIRA, GLAUCIO MONTEIRO; FERREIRA DE SOUZA, ALFREDO DANILO; SANTOS, SORAYA DA SILVA; POSO, ANTTI; RIBEIRO, JOAO AUGUSTO; TAVARES, MAURICIO TEMOTHEO; PAVAN, FERNANDO ROGERIO; GOULART TROSSINI, GUSTAVO HENRIQUE; BERTACINE DIAS, MARCIO VINICIUS; et al. Design, synthesis and biological activity of novel substituted 3-benzoic acid derivatives as MtDHFR inhibitors. Bioorganic & Medicinal Chemistry, v. 28, n. 15, AUG 1 2020. (13/18160-4, 17/00689-0, 13/15906-5, 17/25543-8)

CUNHA, MICAEL RODRIGUES; TAVARES, MAURICIO TEMOTHEO; FERNANDES, THAIS BATISTA; PARISE-FILHO, ROBERTO. Peppers: A ``Hot{''} Natural Source for Antitumor Compounds. Molecules, v. 26, n. 6, MAR 2021. (13/18160-4, 17/00689-0)

VASSILIADES, SANDRA VALERIA; NAVARAUSCKAS, VITOR BASTOS; BERTACINE DIAS, MARCIO VINICIUS; PARISE-FILHO, ROBERTO. Mycobacterium tuberculosis Dihydrofolate Reductase Inhibitors: State of Art Past 20 Years. BIOINTERFACE RESEARCH IN APPLIED CHEMISTRY, v. 13, n. 1, p. 19-pg., 2023-02-15. (17/00689-0, 13/18160-4)

VASSILIADES, SANDRA VALERIA; BORGES, LARA GIMENEZ; GIAROLLA, JEANINE; PARISE-FILHO, ROBERTO. Folate Pathway Inhibitors, An Underestimated and Underexplored Molecular Target for New Anti-tuberculosis Agents. MINI-REVIEWS IN MEDICINAL CHEMISTRY, v. 23, n. 17, p. 22-pg., 2023-01-01. (21/08260-8, 17/00689-0)

FERNANDES, THAIS BATISTA; DE AZEVEDO, RICARDO ALEXANDRE; YANG, ROSANIA; TEIXEIRA, SARAH FERNANDES; GOULART TROSSINI, GUSTAVO HENRIQUE; MARZAGAO BARBUTO, JOSE ALEXANDRE; FERREIRA, ADILSON KLEBER; PARISE-FILHO, ROBERTO. Arylsulfonylhydrazone Induced Apoptosis in MDA-MB-231 Breast Cancer Cells. LETTERS IN DRUG DESIGN & DISCOVERY, v. 15, n. 12, p. 1288-1298, 2018. (13/19311-6, 17/00689-0)

CHAVES, OTAVIO AUGUSTO; TAVARES, MAURICIO TEMOTHEO; CUNHA, MICAEL RODRIGUES; PARISE-FILHO, ROBERTO; SANT'ANNA, CARLOS MAURICIO R.; NETTO-FERREIRA, JOSE CARLOS. Multi-Spectroscopic and Theoretical Analysis on the Interaction between Human Serum Albumin and a Capsaicin Derivative-RPF101. BIOMOLECULES, v. 8, n. 3, SEP 2018. (17/00689-0)

VASCO PEREIRA, GUSTAVO JOSE; TAVARES, MAURICIO TEMOTHEO; AZEVEDO, RICARDO ALEXANDRE; MARTINS, BARBARA BEHR; CUNHA, MICAEL RODRIGUES; BHARDWAJ, RAJESH; CURY, YARA; ZAMBELLI, VANESSA OLZON; BARBOSA, EUZEBIO GUIMARAES; HEDIGER, MATTHIAS A.; et al. Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: Design, synthesis and molecular modeling. Bioorganic & Medicinal Chemistry, v. 27, n. 13, p. 2893-2904, JUL 1 2019. (13/19311-6, 17/00689-0)

SILVA, JOAO VITOR; SANTOS, SORAYA DA SILVA; TERESA MACHINI, M.; GIAROLLA, JEANINE. Neglected tropical diseases and infectious illnesses: potential targeted peptides employed as hits compounds in drug design. Journal of Drug Targeting, v. 29, n. 3, OCT 2020. (17/00689-0)

CUNHA, MICAEL RODRIGUES; BHARDWAJ, RAJESH; CARREL, ALINE LUCIE; LINDINGER, SONJA; ROMANIN, CHRISTOPH; PARISE-FILHO, ROBERTO; HEDIGER, MATTHIAS A.; REYMOND, JEAN-LOUIS. Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor. RSC MEDICINAL CHEMISTRY, v. 11, n. 9, p. 1032-1040, SEP 1 2020. (13/19311-6, 17/00689-0)