The synthesis and antineoplastic activities of thiaziridine, sulfidometylphosphonium, and dithiaphosphitane-sulfide against the Ehrlich ascites carcinoma.

Autor: Mansour ST; Organometallic and Organometalloid Chemistry Department, National Research Centre, Giza, Dokki, Egypt., Hashem AI; Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Abassia, Egypt., Abd-El-Maksoud MA; Organometallic and Organometalloid Chemistry Department, National Research Centre, Giza, Dokki, Egypt., El-Hussieny M; Organometallic and Organometalloid Chemistry Department, National Research Centre, Giza, Dokki, Egypt., El-Makawy AI; Cell Biology Department, National Research Centre, Giza, Dokki, Egypt., Abdel-Aziem SH; Cell Biology Department, National Research Centre, Giza, Dokki, Egypt., Soliman FM; Organometallic and Organometalloid Chemistry Department, National Research Centre, Giza, Dokki, Egypt.
Jazyk: angličtina
Zdroj: Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2022 Jun; Vol. 36 (3), pp. 536-552. Date of Electronic Publication: 2022 Feb 03.
DOI: 10.1111/fcp.12751
Abstrakt: Phosphonium compounds offer an attractive branch of research that chemists and biologists apply for producing many novel drugs for various applications, and its polymeric ingredients are composed of quaternary ammonium and phosphonium salts. The reactions of isothiocyanate with phosphinimine bestow thiaziridine, carbamate, and thiourea derivatives. Moreover, isothiocyanate reacts with tris (dimethylamino) phosphine leading to the formation of sulfidomethyl phosphonium. Lawesson's and Japanese reagents have potential to react with isothiocyanates to generate dithiaphosphetane sulfides. Treatment of isocyanate with Lawesson ' s or Japanese reagents under reflux conditions affords thiaphosphetidinone sulfide, but when applied at room temperature, the dithiaphosphetane sulfide was isolated. Ehrlich ascites carcinoma (EAC) mice model was used to investigate potential anticancer properties of the novel phosphonium and thiophosphate derivatives. Synthesized compounds (100 mg/kg b.w.) were administered orally to the EAC-bearing mice for about 2 weeks. Compounds' antineoplastic activity was determined by the evaluation of volume, viability, and inhibition percent of EAC cells. In addition, DNA fragmentation percent was assessed. The expression of apoptotic marker genes (Bax, Bcl2, Caspase 3) and encoding proinflammatory cytokines (TNF-α) and pro-apoptotic protein (p53) were inspected by real time-quantitative polymerase chain reaction (RT-qPCR). The overall conclusion was based on the findings that treatment with synthesized compounds leads to decrease in tumor volume, increase in tissue DNA fragmentation, downregulation of Bcl2 gene, and upregulation of Bax, caspase3, and p53 markers, along with decrease in TNF-α level in liver tissues. These findings suggest that the anticancer mechanism of these compounds is based on the programmed cell death (Apoptosis).
(© 2022 Société Française de Pharmacologie et de Thérapeutique.)
Databáze: MEDLINE
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