Antitumour, acute toxicity and molecular modeling studies of 4-(pyridin-4-yl)-6-(thiophen-2-yl) pyrimidin-2(1H)-one against Ehrlich ascites carcinoma and sarcoma-180

Dinesh Kumar, Pooja Sharma, Kunal Nepali, Girish Mahajan, Mubashir J. Mintoo, Amarinder Singh, Gurpreet Singh, Dilip M. Mondhe, Gurdarshan Singh, Subheet K. Jain, Girish K. Gupta, Fidele Ntie-Kang

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Abstract

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl) pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC50 value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (EAT, solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile since all 51 computed physicochemical parameters fall within the recommended range for 95% of known drugs. The current study provides insight for further investigation of the antitumour potential of the molecule.

Original languageEnglish
Article numbere00661
JournalHeliyon
Volume4
Issue number6
DOIs
Publication statusPublished - Jun 1 2018
Externally publishedYes

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Keywords

  • Cancer research
  • Pharmaceutical chemistry
  • Pharmaceutical science

ASJC Scopus subject areas

  • General

Cite this

Kumar, D., Sharma, P., Nepali, K., Mahajan, G., Mintoo, M. J., Singh, A., Singh, G., Mondhe, D. M., Singh, G., Jain, S. K., Gupta, G. K., & Ntie-Kang, F. (2018). Antitumour, acute toxicity and molecular modeling studies of 4-(pyridin-4-yl)-6-(thiophen-2-yl) pyrimidin-2(1H)-one against Ehrlich ascites carcinoma and sarcoma-180. Heliyon, 4(6), [e00661]. https://doi.org/10.1016/j.heliyon.2018.e00661