Alam Mahboob, Khan Ajmal, Wadood Abdul, Khan Ayesha, Bashir Shumaila, Aman Akhtar, Jan Abdul Khaliq, Rauf Abdur, Ahmad Bashir, Khan Abdur Rahman, Farooq Umar
Department of Pharmacy, Hazara University Dhodial, Pakistan.
Department of Chemistry, COMSATS Institute of Information Technology Abbottabad, Pakistan.
Front Pharmacol. 2016 Feb 16;7:26. doi: 10.3389/fphar.2016.00026. eCollection 2016.
The main objective of cancer management with chemotherapy (anticancer drugs) is to kill the neoplastic (cancerous) cell instead of a normal healthy cell. The bioassay-guided isolation of two new sesquiterpene coumarins (compounds 1 and 2) have been carried out from Ferula narthex collected from Chitral, locally known as "Raw." Anticancer activity of crude and all fractions have been carried out to prevent carcinogenesis by using MTT assay. The n-hexane fraction showed good activity with an IC50 value of 5.434 ± 0.249 μg/mL, followed by crude MeFn extract 7.317 ± 0.535 μg/mL, and CHCl3 fraction 9.613 ± 0.548 μg/mL. Compounds 1 and 2 were isolated from chloroform fraction. Among tested pure compounds, compound 1 showed good anticancer activity with IC50 value of 14.074 ± 0.414 μg/mL. PASS (Prediction of Activity Spectra) analysis of the compound 1 was carried out, in order to predicts their binding probability with anti-cancer target. As a results the compound 1 showed binding probability with human histone acetyltransferase with Pa (probability to be active) value of 0.303. The compound 1 was docked against human histone acetyltransferase (anti-cancer drug target) by using molecular docking simulations. Molecular docking results showed that compound 1 accommodate well in the anti-cancer drug target. Moreover the activity support cancer chemo preventive activity of different compounds isolated from the genus Ferula, in accordance with the previously reported anticancer activities of the genus.
使用化疗药物（抗癌药物）进行癌症治疗的主要目标是杀死肿瘤细胞而非正常健康细胞。已从奇特拉尔采集的阿魏（当地称为“Raw”）中，通过生物测定引导法分离出两种新的倍半萜香豆素（化合物1和2）。通过MTT试验对粗提物及其所有馏分进行了抗癌活性测试，以预防癌症发生。正己烷馏分表现出良好活性，IC50值为5.434±0.249μg/mL，其次是粗甲醇提取物，IC50值为7.317±0.535μg/mL，氯仿馏分的IC50值为9.613±0.548μg/mL。化合物1和2从氯仿馏分中分离得到。在测试的纯化合物中，化合物1表现出良好的抗癌活性，IC50值为14.074±0.414μg/mL。对化合物1进行了PASS（活性谱预测）分析，以预测其与抗癌靶点的结合概率。结果显示，化合物1与人类组蛋白乙酰转移酶具有结合概率，Pa（活性概率）值为0.303。通过分子对接模拟，将化合物1与人组蛋白乙酰转移酶（抗癌药物靶点）进行对接。分子对接结果表明，化合物1能很好地容纳在抗癌药物靶点中。此外，该活性支持了从阿魏属植物中分离出的不同化合物的癌症化学预防活性，这与该属植物先前报道的抗癌活性一致。
