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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85049019065&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049019065&partnerID=8YFLogxK
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 -
