title: Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines.
abstract: In an attempt to develop potent and selective antitumor agents, a series of novel thiosemicarbazones derived from a natural monoterpene R-(+)-limonene was synthesized and their antitumor activity was evaluated. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of a wide range of cancer cell lines. Almost all of tested thiosemicarbazones were especially sensitive to prostate cells (PC-3). Derivatives 5, 6, 8, 9, 10, 11 and 13 presented the most potent antitumor activity against PC-3 cells. These compounds showed lower value of GI50 (0.04-0.05 μM) than the reference drug paclitaxel, besides a high selectivity for the same cell line. The 4-fluorobenzaldehyde derivative 10 was the most selective compound for prostate cells, while 2-hydroxybenzaldehyde derivative 8 was the most active compound, with potent antitumor activity against all tested cell lines.
authors.affiliation: Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, PR, Brazil. Electronic address: fvandresen@hotmail.com.
authors.forename: Fábio
authors.initials: F
authors.lastname: Vandresen
authors.affiliation: Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, PR, Brazil.
authors.forename: Hugo
authors.initials: H
authors.lastname: Falzirolli
authors.affiliation: Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, PR, Brazil.
authors.forename: Sabrina A
authors.initials: SA
authors.lastname: Almeida Batista
authors.affiliation: Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, PR, Brazil.
authors.forename: Ana Paula B
authors.initials: AP
authors.lastname: da Silva-Giardini
authors.affiliation: Faculdade de Ciências Médicas, Universidade Estadual de Campinas, CEP 13083-877, Campinas, SP, Brazil.
authors.forename: Diogo N
authors.initials: DN
authors.lastname: de Oliveira
authors.affiliation: Faculdade de Ciências Médicas, Universidade Estadual de Campinas, CEP 13083-877, Campinas, SP, Brazil.
authors.forename: Rodrigo R
authors.initials: RR
authors.lastname: Catharino
authors.affiliation: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 6171, CEP 13083-970, Campinas, SP, Brazil.
authors.forename: Ana Lúcia T G
authors.initials: AL
authors.lastname: Ruiz
authors.affiliation: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 6171, CEP 13083-970, Campinas, SP, Brazil.
authors.forename: João E
authors.initials: JE
authors.lastname: de Carvalho
authors.affiliation: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 6171, CEP 13083-970, Campinas, SP, Brazil.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Foglio
authors.affiliation: Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, PR, Brazil. Electronic address: ccsilva@uem.br.
authors.forename: Cleuza Conceição
authors.initials: CC
authors.lastname: da Silva
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053138:Cyclohexenes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D000077222:Limonene; D061986:MCF-7 Cells; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053138:Cyclohexenes; D013729:Terpenes; D013882:Thiosemicarbazones; D000077222:Limonene
keywords: Antitumor; Prostate cancer cells; R-(+)-limonene; Thiosemicarbazide; Thiosemicarbazones