Assessment of an antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in A-549 tumor cell subcutaneous xenografts

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Abstract

Rationale: Chemotherapy is one of the lung cancer treatment methods. The search for new substances with antitumor effect against malignant lung neoplasms is relevant because of low efficacy and side effects of cytotoxic agents. A promising substance class with various biological activities, including antitumor, includes alkaloids of the tropolone family, such as heptamerous non-benzoid aromatic compounds. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)- 5,6,7-trichloro-1,3-tropolone has been synthesized in Institute of Physical and Organic Chemistry; it is a  new compound belonging to 2-quinoline-2-yl derivatives of 1,3-tropolone.

Aim: To assess the antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)- 5,6,7-trichloro-1,3-tropolone on subcutaneous xenografts of A-549 lung tumor cells in immunodeficient Balb/c Nude mice.

Materials and methods: The study included 50  immunodeficient Balb/c Nude mice divided into 4  experimental groups depending on the dosage of the study substance (0.0055, 0.055, 0.55, and 2.75  mg/g); group 5  was the control group. A-549  cells of lung cancer were used as a xenograft. The antitumor effect of tropolone was evaluated by the inhibition of tumor growth and the index of tumor growth. The experiment lasted for 36 days starting from the first administration of the substances.

Results: The mean tumor volumes on day 36  of the experiment in the control group and four experimental groups were 2729.5; 2150.8; 1746.4; 952.3  and 678.9  mm3 , respectively. The indices of tumor growth in groups  1, 2, 3 and 4 were significantly lower than in group 5 (control) starting from days 24, 21, 21 and 15, respectively, and till the end of the experiment. Maximal differences between groups 4 and 5 were observed at days 33 and 36 (by  3.7, p=0.01 and 4.1, p=0.003  times, respectively).

Discussion: The anti-tumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)- 5,6,7-trichloro-1,3-tropolone demonstrated in the study could be related to various mechanisms. For example, numerous studies have shown that its related compound hinokitiol exerts a cytotoxic effect associated with cessation of the cell cycle, apoptosis induction, DNA damage, and autophagic death of tumor cells.

Conclusion: The study demonstrated significant differences in xenograft volumes in all experimental groups, compared to the control group. In mice, 2.75  mg/g bodyweight was the most effective dosage of the studied compound leading to a slow decrease in tumor growth rates and a  decrease in the volumes of subcutaneous xenografts.

About the authors

E. A. Lukbanova

National Medical Research Centre for Oncology

Author for correspondence.
Email: katya.samarskaja@yandex.ru
ORCID iD: 0000-0002-3036-6199

Ekaterina A. Lukbanova – Research Fellow, Experimental Laboratory Center 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

E. V. Zaikina

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0003-0088-2990

Ekaterina V. Zaikina – Junior Research Fellow, Experimental Laboratory Center 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

Yu. A. Sayapin

Federal Research Centre The Southern Scientific Centre of the Russian Academy of Sciences

Email: fake@neicon.ru
ORCID iD: 0000-0002-3180-1762

Yurii A. Sayapin – PhD (in Chem.), Head of Laboratory of Physical Organic Chemistry

41 Chekhova prospekt, Rostov-on-Don, 344006

Russian Federation

E. A. Gusakov

Institute of Physical and Organic Chemistry

Email: fake@neicon.ru
ORCID iD: 0000-0001-7593-1334

Evgeniy A. Gusakov – PhD (in Chem.), Research Fellow 

194/2 Stachki prospekt, Rostov-on-Don, 344090

Russian Federation

S. Yu. Filippova

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-4558-5896

Svetlana Yu. Filippova – Research Fellow, Cell Technologies Laboratory 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

E. Yu. Zlatnik

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-1410-122X

Elena Yu. Zlatnik – MD, PhD, Professor, Chief Research Fellow, Laboratory for Immunophenotyping of Tumors 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

A. V. Volkova

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0001-7823-3865

Anastasia V. Volkova – Junior Research Fellow, Experimental Laboratory Center 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

L. Z. Kurbanova

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0003-3436-1325

Luiza Z. Kurbanova – Junior Research Fellow, Experimental Laboratory Center 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

D. V. Khodakova

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0003-3753-4463

Darya V. Khodakova – Junior Research Fellow, Experimental Laboratory Center 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

D. O. Kaymakchi

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-7556-9897

Dmitriy O. Kaymakchi – Surgeon, Department of Abdominal Oncology No. 2 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

Ju. N. Lazutin

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-6655-7632

Jurij N. Lazutin – Oncologist, Department of Thoracic Surgery 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

A. N. Shevchenko

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-9468-134X

Alexey N. Shevchenko – MD, PhD, Professor, Head of Oncourological Department 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

O. V. Pandova

National Medical Research Centre for Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0003-2218-9345

Olga V. Pandova – Junior Research Fellow, Department of Neuro-oncology 

63 14-ya liniya, Rostov-on-Don, 344037

Russian Federation

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Copyright (c) 2021 Lukbanova E.A., Zaikina E.V., Sayapin Y.A., Gusakov E.A., Filippova S.Y., Zlatnik E.Y., Volkova A.V., Kurbanova L.Z., Khodakova D.V., Kaymakchi D.O., Lazutin J.N., Shevchenko A.N., Pandova O.V.

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