TY - JOUR
T1 - 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
AU - Kumar, Dinesh
AU - Sharma, Pooja
AU - Nepali, Kunal
AU - Mahajan, Girish
AU - Mintoo, Mubashir J.
AU - Singh, Amarinder
AU - Singh, Gurpreet
AU - Mondhe, Dilip M.
AU - Singh, Gurdarshan
AU - Jain, Subheet K.
AU - Gupta, Girish K.
AU - Ntie-Kang, Fidele
N1 - Funding Information:
This work was supported by the University Grants Commission New Delhi, for providing research fellowship under UPE (Focus Area-Health Care, Drug Development and Sports Medicines) Scheme (Sanction No. 25994 /Estt./A-11) to author DK. FNK is currently a Georg Forster (HERMES) fellow of the Alexander von Humboldt Foundation, Germany. The funders played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Publisher Copyright:
© 2018 The Authors
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - Cancer research
KW - Pharmaceutical chemistry
KW - Pharmaceutical science
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U2 - 10.1016/j.heliyon.2018.e00661
DO - 10.1016/j.heliyon.2018.e00661
M3 - Article
AN - SCOPUS:85049019065
SN - 2405-8440
VL - 4
JO - Heliyon
JF - Heliyon
IS - 6
M1 - e00661
ER -
