title: Synthesis and evaluation of novel hybrids β-carboline-4-thiazolidinones as potential antitumor and antiviral agents.
abstract: A series of novel hybrids β-carboline-4-thiazolidinones were synthesized and evaluated for their in vitro antitumor activity against human cancer cell lines and for antiviral activity towards Herpes simplex virus type-1 (HSV-1). From the N'-(2-ylidene-4-thiazolidinone)-β-carboline-3-carbohydrazide series (9-11), compounds 9c and 11d were the most active, showing growth inhibition 50% (GI50) values less than 5 μM for all cell lines tested. Compound 9c, bearing the 4-dimethylaminophenyl group at C-1 of β-carboline was selected for further investigation concerning cell death and cell cycle profile, focusing on the human renal adenocarcinoma cell line 786-0. Treatments with 25 μM of compound 9c induced cell death after 15 h of treatment, characterized by phosphatidylserine exposure and loss of membrane integrity. Moreover, treatment with 12.5 μM promoted a sub-G1 arrest, which indicates cell death. Derivatives of the N-(2-substituted-aryl-4-thiazolidinone)-β-carboline-3-carboxamide series (18-23) showed a potent activity and high selectivity for glioma (U251) and ovarian (OVCAR-3) cancer cell lines. Also, some β-carboline-4-thiazolidinone hybrids showed potent antiviral activity against Herpes simplex virus type-1. The N-(2-substituted-aryl-4-thiazolidinone)-carboxamide moiety in 18, 19 and 22 confer a potent anti-HSV-1 activity for these derivatives, which presented EC50values of 0.80, 2.15 and 2.02 μM, respectively. The assay results showed that the nature of 4-thiazolidinone moiety and of the substituent attached at the 3- and 1- position of β-carboline nucleus influenced the antitumor and antiviral activities.
authors: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900 Maringá, PR, Brazil.
authors: Valéria Aquilino
authors: VA
authors: Barbosa
authors: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900 Maringá, PR, Brazil.
authors: Paula
authors: P
authors: Baréa
authors: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900 Maringá, PR, Brazil.
authors: Renata Sespede
authors: RS
authors: Mazia
authors: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900 Maringá, PR, Brazil.
authors: Tania
authors: T
authors: Ueda-Nakamura
authors: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900 Maringá, PR, Brazil.
authors: Willian Ferreira da
authors: WFD
authors: Costa
authors: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil.
authors: Mary Ann
authors: MA
authors: Foglio
authors: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil.
authors: Ana Lucia T
authors: ALT
authors: Goes Ruiz
authors: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil.
authors: João Ernesto de
authors: JE
authors: Carvalho
authors: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil.
authors: Débora Barbosa
authors: DB
authors: Vendramini-Costa
authors: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900 Maringá, PR, Brazil.
authors: Celso Vataru
authors: CV
authors: Nakamura
authors: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790, 87020-900 Maringá, PR, Brazil. Electronic address: mhsarragiotto@uem.br.
authors: Maria Helena
authors: MH
authors: Sarragiotto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D002243:Carbolines
keywords: 4-Thiazolidinone; Antitumor; Antiviral; β-Carboline