Preclinical studies of steroid-linked nitrosoureas in murine pancreatic adenocarcinoma PANO2.

Abstract

PURPOSE:

In earlier studies, this laboratory carried out research on the synthesis and anticancer evaluation of hybrid compounds, which combine two molecules in one such as homo-aza-steroidal esters (HASE) of carboxylic derivatives of N, N-bis (2-chloroethyl) aniline. In this combination, steroidal hormones are employed as carriers for transporting the alkylating agents to specific targeted tissues. Aiming to continue our research, we used alkylating agents, as nitrosoureas, instead of nitrogen mustards. In this work the N-[N- (2-chloroethyl)-N-nitroso-carbomoyl]-L-alanine (CNC-ala) has been used and was bound to 7 newly synthesized modified steroidal esters (carrier molecule) of nitrosourea and the hybrid molecules were tested for antitumor activity against PANO2 murine pancreatic adenocarcinoma.

MATERIALS AND METHODS:

PANO2 adenocarcinoma was used in this study. C57Bl mice were used for chemotherapy evaluation. The activity was assessed from the inhibition of tumor growth and the oncostatic parameter T/C %.

RESULTS:

The antitumor activity displayed by 7 hybrid steroidal esters of nitrosourea was quite interesting. It was able to discern 4 of 7 compounds that exhibited considerable antitumor activity, increasing the lifespan of the tumor-bearing mice by inhibiting the tumor growth.

CONCLUSION:

The comparative study of 7 newly synthesized hybrid steroidal esters of nitrosourea shows that the antitumor effects of compound 7, which has an enlarged (7 carbon atoms) A-lactamic ring and nitrosourea esterified at the position 17, which seems to be the most appropriate for the connection of a DNA cross-linking amino acid derivative is superior.

• Authors: A Papageorgiou, Th Lialiaris, E Stergiou, I Stergiou, C Tsigris, A Kourti, G Geromichalos, P Stravoravdi, D Trafalis, A E Athanassiou, A Pitsas, Ch Camoutsis
• Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology (J BUON) 2008 Apr-Jun Vol. 13 Issue 2 Pg. 235-9 ISSN: 1107-0625 [Print] Cyprus
• PMID: 18555471 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Nitrogen Mustard Compounds
• Nitrosourea Compounds
• Steroids
• N-(2-chloroethyl)-1-nitrosocarbamoylalanine
• Alanine

Topics

• Adenocarcinoma (drug therapy, secondary)
• Alanine (analogs & derivatives, chemistry)
• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Pancreatic Ductal (secondary)
• Drug Evaluation, Preclinical
• Female
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Structure
• Nitrogen Mustard Compounds (chemistry)
• Nitrosourea Compounds (chemical synthesis, therapeutic use)
• Pancreatic Neoplasms (drug therapy, pathology)
• Steroids (chemistry, pharmacology)
• Survival Rate
• Tumor Cells, Cultured