ORIGINAL RESEARCH
Benzimidazole derivative as antitumor drug against experimentally induced lung carcinoma
1 National Medical Research Center of Oncology, Rostov-on-Don, Russia
2 Rostov State Medical University, Rostov-on-Don, Russia
3 Research Institute for Physical and Organic Chemistry of Southern Federal University, Rostov-on-Don, Russia
Correspondence should be addressed: Ekaterina A. Lukbanova
Azovskaya, 163, 346783, Azov; ur.xednay@ajaksramas.aytak
Funding: synthesis of the tested compound was supported by the Russian Ministry of Science and Higher Education under the state assignment for the Southern Federal University, 2020, Project FENW-2020-0031 (0852-2020-0031). In vivo experiments were part of the state assignment Study of antitumor activity of pharmacological substances in vivo and in vitro (121031100253-3).
Author contributions: Komarova EF proposed the design, conducted the experiment and wrote the draft version of the manuscript; Zhukovskaya ON synthesized the tested compound and edited the manuscript; Lukbanova EA conducted the experiment and contributed to writing the manuscript; Yengibaryan MA edited the manuscript; Vashenko LN proposed the concept and design for the study, edited the manuscript; Kharagezov DA contributed to writing the manuscript; Pozdnyakova VV performed statistical analysis; Ushakova ND proposed the concept and design for the study; Shatova YuS prepared the list of references and edited the manuscript; Przhedetsky YuV performed technical editing.
Compliance with ethical standards: the study was approved by the Ethics Committee of National Medical Research Center for Oncology (Protocol № 18 dated September 10, 2015); the experiment complied with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes.
Most cancer drugs used in a clinical setting are insufficiently effective and insufficiently safe. This prompts the search for novel substances to fight cancer. The aim of this study was to explore the effects of dihydrobromide 2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo[1,2-a] benzimidazole (RU-185) on the growth and metastasis of experimentally induced transplantable Lewis lung carcinoma (LLC). Fifty-five C57/Bl6 male mice (weight 18–20 g) were subcutaneously inoculated with LLC cells. The tested substance (0.5 ml) was administered intragastrically at 50, 220, and 500 mg/kg (groups 1, 2 and 3, respectively) once a day for 10 days starting at 48 h after inoculation. The control group received normal saline. Intragastric administration of the tested substance resulted in significantly longer survival in group 2 only (162.3%) and in the significant reduction of tumor size on day 1 after treatment in all groups. After the end of treatment, tumor sizes in groups 2 and 3 were 3.4 and 1.3 times smaller, respectively, on day 7 and 2.2. and 1.3 times smaller, respectively, on day 14 than in the control group (р < 0,05). The growth delay rate was sustained in group 2 by day 14 after the end of treatment; tumor regression was observed in 20% of the animals. The number of metastases in the lungs was lower in groups 1 and 2 than in the control group (2.6 and 3.1-fold, respectively), and the metastasis inhibition was 68.1% and 80%, respectively. The tested substance RU-185 has an anticancer effect in mice: it results in longer survival, slower growth of the primary tumor and fewer lung metastases of Lewis lung carcinoma.
Keywords: Lewis lung carcinoma, antitumor activity, antimetastatic activity, intragastric administration, RU-185