Kumar Sanjiv, Lim Siong Meng, Ramasamy Kalavathy, Vasudevan Mani, Shah Syed Adnan Ali, Selvaraj Manikandan, Narasimhan Balasubramanian
Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.
Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
Chem Cent J. 2017 Sep 18;11(1):89. doi: 10.1186/s13065-017-0322-0.
Heterocyclic pyrimidine nucleus, which is an essential base component of the genetic material of deoxyribonucleic acid, demonstrated various biological activities. A series of bis-pyrimidine Schiff bases were synthesized and screened for its antimicrobial and anticancer potentials. The molecular docking study was carried to find the interaction between active molecules with receptor.
The structures of synthesized bis-pyrimidine Schiff bases were confirmed by spectral studies. The synthesized bis-pyrimidine derivatives were evaluated for their antimicrobial activity (MIC = µmol/mL) against selected Gram positive; Gram negative bacterial and fungal strains by tube dilution method. The anticancer activity (IC = µmol/mL) of the synthesized compounds was determined against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B (SRB) assay. Molecular docking studies provided information regarding the binding mode of active bis-pyrimidine Schiff bases with the cyclin-dependent kinase 8 (CDK8) receptor.
The antimicrobial screening results indicated that compounds, q1 (MIC = 0.83 µmol/mL), q16 (MIC = 1.54 µmol/mL and MIC = 0.77 µmol/mL), q1 and q19 (MIC = 0.41 µmol/mL) and q20 (MIC = 0.36 µmol/mL) are the most active ones. Compounds q1 (IC = 0.18 µmol/mL) have emerged as potent anticancer molecule against human colorectal carcinoma cancer cell line than the reference drug, 5-fluorouracil. Molecular docking studies indicated that compound q1 (the most active molecule) has the maximum hydrogen bond interaction (four) and π-π stacking (three) network among the bis-pyrimidine Schiff bases. Graphical abstract Graphical illustration of predicted binding mode of bis-pyrimidine Schiff bases in the active site of CDK8. a. Compound 1 (magenta color), b. Compound 5 (green color), c. Compound 8 (red color), d. Compound 13 (split pea color).
杂环嘧啶核是脱氧核糖核酸遗传物质的重要碱基组成部分，具有多种生物活性。合成了一系列双嘧啶席夫碱，并对其抗菌和抗癌潜力进行了筛选。进行了分子对接研究以发现活性分子与受体之间的相互作用。
通过光谱研究证实了合成的双嘧啶席夫碱的结构。采用试管稀释法对合成的双嘧啶衍生物针对选定的革兰氏阳性菌、革兰氏阴性菌和真菌菌株进行了抗菌活性评估（MIC = μmol/mL）。通过磺酰罗丹明B（SRB）测定法测定了合成化合物对人结肠癌细胞系（HCT116）的抗癌活性（IC = μmol/mL）。分子对接研究提供了有关活性双嘧啶席夫碱与细胞周期蛋白依赖性激酶8（CDK8）受体结合模式的信息。
抗菌筛选结果表明，化合物q1（MIC = 0.83 μmol/mL）、q16（MIC = 1.54 μmol/mL和MIC = 0.77 μmol/mL）、q1和q19（MIC = 0.41 μmol/mL）以及q20（MIC = 0.36 μmol/mL）是活性最高的。与参考药物5-氟尿嘧啶相比，化合物q1（IC = 0.18 μmol/mL）已成为针对人结肠癌细胞系的有效抗癌分子。分子对接研究表明，化合物q1（活性最高的分子）在双嘧啶席夫碱中具有最大的氢键相互作用（四个）和π-π堆积（三个）网络。图形摘要双嘧啶席夫碱在CDK8活性位点的预测结合模式的图形说明。a. 化合物1（品红色），b. 化合物5（绿色），c. 化合物8（红色），d. 化合物13（豌豆色）。
