Silver(I) complexes of 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazones and triphenylphosphine: structural, cytotoxicity, and apoptotic studies

Autor(es)

Silva, Debora E. S. ^[1] ; Becceneri, Amanda B. ^[2] ; Santiago, Joao V. B. ^[1] ; Gomes Neto, Jose A. ^[1] ; Ellena, Javier ^[3] ; Cominetti, Marcia R. ^[2] ; Pereira, Jose C. M. ^[1] ; Hannon, Michael J. ^[4] ; Netto, Adelino V. G. ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Sao Paulo State Univ, Inst Chem, Dept Gen & Inorgan Chem, Dept Analyt Chem, BR-14800060 Araraquara, SP - Brazil

^[2] Univ Fed Sao Carlos, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[3] Univ Sao Paulo, Sao Carlos Inst Phys, BR-13566590 Sao Carlos, SP - Brazil

^[4] Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands - England

• Tipo de documento: Artigo Científico
• Fonte: DALTON TRANSACTIONS; v. 49, n. 45, p. 16474-16487, DEC 7 2020.
• Citações Web of Science: 1

Resumo

Novel silver(i) complexes of the type {[}AgCl(PPh3)(2)(L)] [PPh3 = triphenylphosphine; L = VTSC = 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazone (1); VMTSC = 3-methoxy-4-{[}2-(morpholine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (2); VPTSC = 3-methoxy-4-{[}2-(piperidine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (3)] were synthesized and fully characterized by spectroscopic techniques. The molecular structures of complexes 2 and 3 were determined by single crystal X-ray diffraction. Compounds 1-3 exhibited appreciable cytotoxic activity against human tumor cells (lung A549, breast MDA-MB-231 and MCF-7) with IC50 values in 48 h of incubation ranging from 5.6 to 18 mu M. Cellular uptake studies showed that complexes 1-3 were efficiently internalized after 3 hours of treatment in MDA-MB-231 cells. The effects of complex 1 on the cell morphology, cell cycle, induction of apoptosis, mitochondrial membrane potential (Delta psi(m)), and reactive oxygen species (ROS) production have been evaluated in triple negative breast cancer (TNBC) cells MDA-MB-231. Our results showed that complex 1 induced typical morphological alterations of cell death, an increase in cells at the sub-G1 phase, apoptosis, and mitochondrial membrane depolarization. Furthermore, DNA binding studies evidenced that 1 can bind to ct-DNA and does so without modifying the B-structure of the DNA, but that the binding is weak compared to that of Hoechst 33258. (AU)

• Processo FAPESP: 13/26203-5 - Compostos quadráticos planos contendo 3,3'-biisoquinolina: síntese e investigação da interação frente aos G-quadruplexos de DNA
• Beneficiário: Adelino Vieira de Godoy Netto
• Modalidade de apoio: Bolsas no Exterior - Pesquisa