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
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
Sri Sai College of Pharmacy Manawala, Amritsar, 143115, Punjab, India.
Heliyon. 2018 Jun 27;4(6):e00661. doi: 10.1016/j.heliyon.2018.e00661. eCollection 2018 Jun.
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(1)-one (), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of 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, 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.
为了发现一种有效且具有选择性的抗肿瘤药物，我们对4-(吡啶-4-基)-6-(噻吩-2-基)嘧啶-2(1)-酮（）进行了合成及抗癌潜力研究。我们之前已报道该化合物对MiaPaCa-2恶性细胞具有显著的细胞毒性，IC值为1.95 μM，且能诱导细胞凋亡。在本研究中，我们考察了该化合物对艾氏腹水瘤（EAT，实体瘤）、肉瘤180（实体瘤）和艾氏腹水癌的抗肿瘤效果。结果发现，在30 mg/kg剂量下，该化合物对艾氏腹水癌（EAC）的肿瘤生长抑制率为94.71%，对艾氏肿瘤（ET，实体瘤）为59.06%，对肉瘤180（实体瘤）为45.68%。此外，在瑞士白化小鼠的急性口服毒性实验中，该化合物在最大耐受剂量1000 mg/kg时被确定为无毒。基于计算机的预测还表明，该化合物可能具有有趣的药物代谢动力学特征，因为所有51个计算得到的物理化学参数都落在95%已知药物的推荐范围内。本研究为进一步研究该分子的抗肿瘤潜力提供了思路。
