Study of antitumor activity of 2-quinoline-2-yl-derivative 1,3-tropolone in PDX models of lung cancer.

Abstract

e20523 Background: The purpose of the study was to reveal the antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in subcutaneous PDX models of human non-small cell lung cancer (NSCLC). Methods: The studied tropolone was synthesized using a method of expanding the o-quinone cycle. Acute tropolone toxicity was evaluated by the survival and changes in the health status of female Balb/c Nude mice. Antitumor tropolone effects were studied in subcutaneous patient-derived xenograft (PDX) models of human squamous cell lung cancer in Balb/c Nude mice. The average volumes of tumor nodes and tumor growth inhibition (TGI%) rate were taken into account. Biochemical blood tests and histological analysis of the tumor material were performed in recipient mice. Results: An analysis of acute tropolone toxicity did not reveal the lethal dose. The maximal TGI, 73.5% for females and 74.4% for males, was observed on day 36 of the experiment in group 5 which received 2.75 mg/g tropolone. The average tumor volumes in females of this group were 431.3 mm3 on day 33 of the experiment, in males – 428.9 mm3 on day 30, and then the tumor volumes declined. Biochemical blood tests and histological analysis of the tumor material in recipient mice confirmed the tendency demonstrated during the analysis of the TGI dynamics, which in turn was the result of the dose-dependent antitumor effect of the studied tropolone. Conclusions: The research demonstrated the antitumor activity of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone against subcutaneous PDX models of human NSCLC. The revealed tendencies can be used to search for effective modes of the compound application in clinical practice.