Design, synthesis and antitumor activity of aryl-sulfonylhydrazone compounds

• Grant number: 13/19311-6
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2014
• Effective date (End): July 31, 2015
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Roberto Parise Filho
• Grantee: Thais Batista Fernandes
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is a leading cause of death all over the world and was responsible for 7.6 million deaths in 2008. This situation imposes an urgent development of more selective and less toxic anticancer agents. Advances in this field led the isolation of capsaicin, a primary pungent compound in red peppers, which has antitumor activity. In this regard, our group reported a synthetic capsaicin-like analogue, RPF101, which presents higher in vitro antitumor activity than its prototype. Previous studies revealed that substances containing a sulfonyl-hydrazone moiety were also able to inhibit tumors in vivo. Thus, the aim of this work is to optimize RPF101 activity by the synthesis of hybrid RPF101/sulfonyl-hydrazone-based compounds. The analogues will be synthesized in three reaction steps, based in mechanisms of substitution and addition. Moreover, these compounds will be evaluated for their cytotoxic potential in breast tumor cell lines (MDA-MB-231 and MCF-7). The most promising product will be further evaluated in order to elucidate mechanistic properties. In parallel, studies of quantitative structure-activity relationship (QSAR) will be carried out, for the purpose of to investigate molecular properties of the compounds and correlate these informations with biologic data. In this context, it is expected to develop new anticancer agents, in order to obtain better therapeutic options for current cancer treatment.

Scientific publications

(5)

(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)

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)

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)

FERNANDES, THAIS B.; CUNHA, MICAEL R.; SAKATA, RENATA P.; CANDIDO, THALITA M.; BABY, ANDRE R.; TAVARES, MAURICIO T.; BARBOSA, EUZEBIO G.; ALMEIDA, WANDA P.; PARISE-FILHO, ROBERTO. Synthesis, Molecular Modeling, and Evaluation of Novel Sulfonylhydrazones as Acetylcholinesterase Inhibitors for Alzheimer's Disease. ARCHIV DER PHARMAZIE, v. 350, n. 11, NOV 2017. (13/19311-6)

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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FERNANDES, Thais Batista. Design, synthesis and antitumor evaluation of arylsulfonylhydrazone compounds.. 2015. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.