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
Affiliations
Dinesh Kumar
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India; Sri Sai College of Pharmacy Manawala, Amritsar, 143115, Punjab, India; Corresponding authors.
Pooja Sharma
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India; Sri Sai College of Pharmacy Manawala, Amritsar, 143115, Punjab, India
Kunal Nepali
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India
Girish Mahajan
CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Canal Road, Jammu 180001, India
Mubashir J. Mintoo
CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Canal Road, Jammu 180001, India
Amarinder Singh
CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Canal Road, Jammu 180001, India
Gurpreet Singh
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India
Dilip M. Mondhe
CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Canal Road, Jammu 180001, India
Gurdarshan Singh
CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Canal Road, Jammu 180001, India
Subheet K. Jain
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India
Girish K. Gupta
Department of Pharmaceutical Chemistry, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, New Delhi, Haryana, India
Fidele Ntie-Kang
Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon; Institute for Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany; Department of Informatics and Chemistry, University of Chemistry and Technology Prague, Technická 5 166 28 Prague 6, Dejvice, The Czech Republic; Corresponding authors.
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.
