ORIGINAL RESEARCH

Benzimidazole derivative as antitumor drug against experimentally induced lung carcinoma

Komarova EF1,2, Zhukovskaya ON3, Lukbanova EA, Yengibaryan MA, Vashenko LN1, Kharagezov DA1, Pozdnyakova VV, Ushakova ND, Shatova YuS, Przhedetsky YuV
About authors

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

About paper

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.

Received: 2021-06-01 Accepted: 2021-06-15 Published online: 2021-06-25
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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

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