Study of biological activity of 2-quinoline-2-yl-derivative 1,3-tropolone in experiment

Abstract

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 lung cancer.Material and methods. The studied tropolone was synthesized using a method of expanding the o‑quinone cycle. Assess to it’s toxic effects was given 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 toxic effects did not reveal the lethal dose. The maximal TGI was observed on day 36 of the experiment in group 5 which have received 2.75 mg/g tropolone and accounted 73.5 % for females and 74.4 % for males. The average tumor volumes in females of this group were 431.3 ± 1,1 mm3 on day 33 of the experiment, in males – 428.9 ± 1,7 mm3 on day 30, and then the tumor volumes declined. The biochemical analysis of blood and histological examination of the tumor tissue of recipient mice reflect the severity of the antitumor effect on the dose of the studied tropolone.Conclusion. 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.

Keywords

• tropolones
• antitumor activity
• balb/c nude mice
• xenograft
• dose dependent effects
• toxic effect
• non-small-cell lung carcinoma (nsclc)