Synthesis, antiproliferative activity in cancer cells and theoretical studies of novel 6α,7β-dihydroxyvouacapan-17β-oic acid Mannich base derivatives.
Natural products are great prototypes for the design of new anticancer agents. The plant-derived natural product 6α,7β-dihydroxyvouacapan-17β-oic acid (1) is promising for the development of more potent antiproliferative agents against human cancer cells. Indeed, its lactone derivative 6α-hydroxyvouacapan-7β,17β-lactone (2), a non-natural furanoditerpene, exhibited higher anticancer activity than compound 1. Herein, we describe the synthesis and antiproliferative activity of six new Mannich derivatives of compound 2 against nine cancer cell lines. Overall, our results revealed that Mannich derivatives 3-8 were more potent than compound 2 in inhibiting the proliferation of cancer cells. Theoretical studies also supported our findings, revealing the nucleophilic character of furan ring as an important feature for antiproliferative activity of the studied Mannich derivatives.
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Felipe P G
FP
Euzébio
Flávio J L dos
FJ
Santos
Dorila
D
Piló-Veloso
Antônio F C
AF
Alcântara
Ana L T G
AL
Ruiz
João Ernesto de
JE
Carvalho
Mary A
MA
Foglio
Dalton L
DL
Ferreira-Alves
Angelo de
Ad
Fátima
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D007887:Fabaceae / Q000737:chemistry; D005638:Fruit / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D006801:Humans; D007783:Lactones / Q000737:chemistry; D008352:Mannich Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D011789:Quantum Theory
D000970:Antineoplastic Agents; D004224:Diterpenes; D005663:Furans; D007783:Lactones; D008352:Mannich Bases; C073437:vouacapan