A novel second-generation platinum derivative and evaluation of its anti-cancer potential
Küçük Resim Yok
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Univ Sao Paulo, Conjunto Quimicas
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Cisplatin is the primary anti-cancer agent for the treatment of most solid tumors. However, platinum-based anti-cancer chemotherapy produces severe side effects due to its poor specificity. There are a broad interest and literature base for a novel mechanism of action on platinum derivatives. Additionally, combining cisplatin with histone deacetylase inhibitors (HDACi) such as 4-hydroxybenzoic acid derivatives showed promising results in treating solid tumors. Here we aimed to conjugate 4-hydroxybenzoic acid with platinum to obtain a novel platinum derivative that can overcome cisplatin resistance. Cis-4-hydroxyphenylplatinum(II)diamine compound was synthesized under mild conditions and characterized. Cytotoxicity assay was performed on SKOV3-Luc and A549-Luc cells. Hemocompatibility and serum protein binding analysis were performed. Treatment potential was evaluated in xenograft tumor models. Biodistribution was tested on tumor-bearing mice via Pt analysis in organs with ICP-MS, ex vivo. In this study, cis-4-hydroxyphenylplatinum (II) diamine was synthesized with a yield of 62%. The MTT assay on A549-Luc and SKOV3-Luc cell lines resulted in IC50 values of 17.82 and 7.81 mu M, respectively. While tumor growth was continued in the control group, the tumor volume decreased in the treatment group. All results point to the conclusion that the new compound has the potential to treat solid tumors.
Açıklama
Anahtar Kelimeler
Platinum-Derivative, 4-Hydroxybenzoic Acid, Anti-Cancer Agent, Xenograft Model, Lung Cancer, Protein-Binding, Cisplatin, Tissues, Plasma, Acid
Kaynak
Brazilian Journal Of Pharmaceutical Sciences
WoS Q Değeri
Q4
Scopus Q Değeri
Cilt
58
