Study of Hantzsch multicomponent reaction for the synthesis of new dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type II Diabetes

• Grant number: 16/18045-9
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2017
• End date: March 31, 2020
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Mirela Inês de Sairre
• Grantee: Mirela Inês de Sairre
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated researchers: Kathia Maria Honorio ; Paulo Marcos Donate ; Raquel Alves dos Santos ; Shirley Muniz Machado Rodrigues ; Wagner Alves Carvalho
• Associated scholarship(s): 18/03069-5 - General technical assistance at the laboratory of Chemical Biology of UFABC, BP.TT

Abstract

Type II Diabetes mellitus (T2DM) disease is the most prevalent form of diabetes and the International Diabetes Federation (IDF) estimates that the number of diagnosed cases reach 642 million people by 2040. The individual with T2DM has insulin resistance and often the clinical picture worsens by hyperlipidemia and inflammation. Although there are several drugs available with different action mechanisms, there is still a need to find new therapeutic agents because most treatments cause adverse effects and possible complications to the patient. Dipeptidyl peptidase 4 (DPP-4) inhibitors constitute a new class of drugs for the treatment of T2DM and this work we pretend to synthesise new molecules that can act as DPP-4 effective inhibitors. The molecules are substituted pyridines and were designed from computational studies. According to the synthetic methodology, studies on the Hantzsch multicomponent reaction (MCR) and preparation of tetrazoles will be performed. Different niobium catalysts will be tested in the MCR to find suitable reaction conditions and synthetic viability. This project is inserted in the scientific and technological development in drug design with interest of the pharmaceutical industry, medicine and the productive sector. (AU)

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)

VIGATO, ARYANE A.; MACHADO, IAN P.; DEL VALLE, MATHEUS; DA ANA, PATRICIA A.; SEPULVEDA, ANDERSON F.; YOKAICHIYA, FABIANO; FRANCO, MARGARETH K. K. D.; LOIOLA, MESSIAS C.; TOFOLI, GIOVANA R.; CEREDA, CINTIA MARIA S.; et al. onoketonic Curcuminoid-Lidocaine Co-Deliver Using Thermosensitive Organogels: From Drug Synthesis to Epidermis Structural Studie. HARMACEUTIC, v. 14, n. 2, FEB 2022. (19/20303-4, 16/18045-9, 19/14773-8)

VIGATO, ARYANE ALVES; QUEROBINO, SAMYR MACHADO; DE FARIA, NAIALLY CARDOSO; BOLELA BOVO CANDIDO, ANA CAROLINA; MAGALHAES, LIZANDRA GUIDI; SAIA CEREDA, CINTIA MARIA; TOFOLI, GIOVANA RADOMILLE; RAMOS CAMPOS, ESTEFANIA VANGELIE; MACHADO, IAN POMPERMAYER; FRACETO, LEONARDO FERNANDES; et al. Physico-Chemical Characterization and Biopharmaceutical Evaluation of Lipid-Poloxamer-Based Organogels for Curcumin Skin Delivery. FRONTIERS IN PHARMACOLOGY, v. 10, SEP 12 2019. (18/04036-3, 16/24456-1, 16/18045-9, 18/02482-6, 14/14457-5)

SOUZA, JULIA M.; DE CARVALHO, ERICA A. A.; CANDIDO, ANA CAROLINA B. B.; DE MENDONCA, RAFAEL P.; FERNANDA DA SILVA, MARIA; PARREIRA, RENATO L. T.; DIAS, FERNANDA G. G.; AMBROSIO, SERGIO R.; ARANTES, ANDREA T.; DA SILVA FILHO, ADEMAR A.; et al. Licochalcone a Exhibits Leishmanicidal Activity in vitro and in Experimental Model of Leishmania (Leishmania) Infantum. FRONTIERS IN VETERINARY SCIENCE, v. 7, DEC 10 2020. (13/11164-4, 16/18045-9, 16/24456-1)

PANTALEAO, SIMONE QUEIROZ; PHILOT, ERIC ALLISON; ALMEIDA, MICHELL DE OLIVEIRA; LIMA, ANGELICA NAKAGAWA; DE SAIRRE, MIRELA INES; SCOTT, ANA LIGIA; HONORIO, KATHIA MARIA. Integrated Protocol to Design Potential Inhibitors of Dipeptidyl Peptidase-4 (DPP-4). CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 20, n. 3, p. 209-226, 2020. (16/18045-9, 16/24524-7, 17/10118-0, 15/20314-5)

BADOCO, FERNANDA R.; PAULA, LUCAS A. L.; ORENHA, RENATO P.; MENDES, TIAGO M. F.; SQUARISI, IARA S.; EL-SAKKARY, NELLY; LOIOLA, MESSIAS C.; KATZ, NAFTALE; TAVARES, DENISE C.; SAIRRE, MIRELA I.; et al. EF24, a schistosomicidal curcumin analog: Insights from its synthesis and phenotypic, biochemical and cytotoxic activities. Chemico-Biological Interactions, v. 368, p. 11-pg., 2022-10-13. (17/24856-2, 18/50011-2, 15/01394-8, 14/02018-7, 16/18045-9, 16/24456-1)