Intraperitoneal administration of dihydrobromide-2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo-[1,2-a]benzimidazole has an antitumor effect against syngeneic tumors of melanoma and lung.
Authors: Goncharova Anna S. , Komarova Ekaterina Fedorovna , Verenikina Ekaterina V. , Shevchenko Nataliya , Engibaryan Marina A. , Volkova Viktoriya L. , Pustovaya Irina V. , Chertova Natalia A. , Cherkes Maria A. , Bauzhadze Mamuka V. , Goncharova Elena G. , Gvaramiya Astanda K. , Ulianova Yulia V. , Maldonado Mary L. , Komarova Elizaveta , Galina A. V. 
Published: June 2022

e21568 Background: Despite the wide range of modern drugs for cancer drug therapy, there is still a problem of their high toxicity, which leads to the search for antitumor agents that selectively suppress or inhibit the growth of neoplastic cells. Over the past decades, many benzimidazole derivatives have been reported with potent antitumor activity due to its structural similarity to naturally occurring nucleotides. The aim is to study the effect of dihydrobromide-2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo-[1,2-a]benzimidazole on the growth and metastasis of transplantable experimental tumors after intraperitoneal administration. Methods: Melanoma B16 and Lewis lung carcinoma (LLC) were inoculated subcutaneously into 96 female C57/Bl6j mice (weighing 18–20 g). Intraperitoneal (0.3 ml/day) administration of the drug was carried out 48 hours after tumor inoculation 1 time per day for 10 days in single doses of 6.15 (1st), 30.75 (2nd) and 61.5 (3 -i) mg/kg. The control group of animals was injected with saline. The increase in life expectancy (T/C,%), the degree of tumor growth inhibition (TGI,%) and the metastasis inhibition index (MII,%) were calculated. Results: With intraperitoneal administration of 2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo[1,2-a]benzimidazole at a dose of 30.75 mg/kg, it increased the lifespan of animals with B16 (T/C = 151.3%). On the 7th day after the end of treatment in the 1st (6.15 mg/kg) and 2nd groups (30.75 mg/kg) a slight decrease in the volume of the primary tumor B16 was found, which remained by the 14th day only in 2 -th group (TGI = 23.6%). Also for LLC in the 30.75 mg/kg dose group, the T/C index was 171.6%. The volume of the primary subcutaneous tumor node was already 2.3 times lower on the 1st day after the end of treatment compared to the control (p < 0.05) and this effect persisted up to the 14th day (the tumor volume was reduced by 2. 1 and 1.9 times on the 7th and 14th days, respectively, at p < 0.05). In groups with B16, the use of the substance reduced the number of metastases in the 1st and 2nd groups by 2.5 and 3.0 times, respectively (p < 0.05), relative to the control. The frequency of metastasis was in the 1st group B16 -60.4%, and in the 2nd - 74.5%. Similar results of antimetastatic activity were shown for LLC: the number of metastases in the 1st and 2nd groups was reduced by 2.1 and 2.6 times, respectively (p < 0.05) compared with the control. MII was higher for LLC compared to B16 and amounted to 63.1 and 79.6 in groups for groups 1 and 2, respectively. Conclusions: When administered intraperitoneally, 2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo[1,2-a]benzimidazole dihydrobromide showed an antitumor effect against primary Lewis lung carcinoma and its lung metastases, as well as against lung metastases for melanoma B16 mice.