In vivo Antitumor, Pharmacological and Toxicological Study of Pyrimido[ 4′,5′:4,5] thieno(2,3-b)quinoline with 9-hydroxy-4-(3-diethylaminopropylamino) and 8-methoxy-4-(3-diethylaminopropylamino) Substitutions

(E-pub Ahead of Print)

Author(s): Hulihalli N. KiranKumar, Heggodu G. RohitKumar, Ajay S. Khandagale, Gopal M. Advirao*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

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Background: We previously synthesized two DNA intercalative pyrim-ido[4’,5’:4,5]thieno(2,3-b) quinolines (PTQ), 9-hydroxy-4-(3-diethylaminopropylamino)pyrimido[4’,5’:4,5]thieno(2,3-b) quinolines (Hydroxy-DPTQ) and 8-methoxy-4-(3-diethylaminopropylamino) pyrimido[4’,5’:4,5]thieno(2,3-b) quinolines (Methoxy-DPTQ), and reported their cytotoxicity against cancer cell lines.

Objective: In the present study, we sought to analyze the antitumor activity of Hydroxy-DPTQ and Methoxy-DPTQ on Ehrlich’s ascites carcinoma in vivo models, along with other pharmacological activities and toxicity.

Methods: Antitumor activity, In vivo antioxidant measurement, Anti-inflammatory activity Analgesic activity, Hematological study, Biochemical parameters, and Nephroprotective ac-tivity.

Results: In this study, both the test molecules studied possess potent in vivo antitumor activi-ty without any hematological, biochemical or nephrotoxicity. Significant tumor regression was observed after treatment with both the test molecules, which is suggested by the decrease in the body weight of tumor bearing mice. Mean survival time of mice with tumor was increased from 16 days to 25 and 29 days after 40 and 80 mg/kg Hydroxy-DPTQ treatment, respectively, with a similar result for Methoxy-DPTQ. A dose dependent increase in lifespan upto 80-85% was also displayed by both Hydroxy-DPTQ and Methoxy-DPTQ. Reduction in the tumor volume of mice, upon treatment with molecules also confirmed their antitumor activity. These molecules also exhibited pharmacological activities such as antioxidant, anti-inflammatory and analgesic activities. Administration of Hydroxy-DPTQ and Methoxy-DPTQ not only reduced the level of lipid peroxidation in tumor bearing mice, but also restored the superoxide dismutase, glutathione and catalase levels to normal, substantiating the antioxidant property. Also, treatment of Hydroxy-DPTQ and Methoxy-DPTQ inhibited the pain to approximately 60-80% and 19-33%, respectively. Further, the treatment with Hydroxy-DPTQ and Methoxy-DPTQ reversed the abnormality in the RBC, WBC and haemoglobin levels, and gentamicin induced nephrotoxicity.

Conclusion: Hydroxy-DPTQ and Methoxy-DPTQ are good antitumor molecules with phar-macological properties.

Keywords: Antitumor activity, toxicity, pharmacological activity, ehrlich ascites carcinoma, antioxidant, pyrimido[4’, 5’:4, 5]thieno(2, 3-b)quinolines

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Article Details

Published on: 08 February, 2021
(E-pub Ahead of Print)
DOI: 10.2174/1871520621666210208175609
Price: $95

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