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

Research output: Contribution to journalArticle

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

Fingerprint

Sarcoma 180
Ascites
Ehrlich Tumor Carcinoma
Carcinoma
Neoplasms
Maximum Tolerated Dose
Antineoplastic Agents
Inhibitory Concentration 50
Apoptosis
Pharmaceutical Preparations

Keywords

  • Cancer research
  • Pharmaceutical chemistry
  • Pharmaceutical science

ASJC Scopus subject areas

  • General

Cite this

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

In: Heliyon, Vol. 4, No. 6, e00661, 01.06.2018.

Research output: Contribution to journalArticle

Kumar, D, Sharma, P, Nepali, K, Mahajan, G, Mintoo, MJ, Singh, A, Singh, G, Mondhe, DM, Singh, G, Jain, SK, Gupta, GK & 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, vol. 4, no. 6, e00661. https://doi.org/10.1016/j.heliyon.2018.e00661
Kumar, Dinesh ; Sharma, Pooja ; Nepali, Kunal ; Mahajan, Girish ; Mintoo, Mubashir J. ; Singh, Amarinder ; Singh, Gurpreet ; Mondhe, Dilip M. ; Singh, Gurdarshan ; Jain, Subheet K. ; Gupta, Girish K. ; Ntie-Kang, Fidele. / 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. In: Heliyon. 2018 ; Vol. 4, No. 6.
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