Pavlović Ivan, Petrović Silvana, Milenković Marina, Stanojković Tatjana, Nikolić Dejan, Krunić Aleksej, Niketić Marjan
University of Belgrade - Faculty of Pharmacy, Department of Pharmacognosy, Vojvode Stepe 450, RS-11221 Belgrade, (phone: +381-11-3951322; fax: +381-11-3972840).
University of Belgrade - Faculty of Pharmacy, Department of Microbiology and Immunology, Vojvode Stepe 450, RS-11221 Belgrade.
Chem Biodivers. 2015 Oct;12(10):1585-94. doi: 10.1002/cbdv.201400400.
The antimicrobial and cytotoxic activities of isolates (CHCl3 and MeOH extracts and selected metabolites) obtained from the underground parts of the Balkan endemic plant Ferula heuffelii Griseb. ex Heuff. were assessed. The CHCl3 and MeOH extracts exhibited moderate antimicrobial activity, being more pronounced against Gram-positive than Gram-negative bacteria, especially against Staphylococcus aureus (MIC=12.5 μg/ml for both extracts) and Micrococcus luteus (MIC=50 and 12.5 μg/ml, resp.). Among the tested metabolites, (6E)-1-(2,4-dihydroxyphenyl)-3,7,11-trimethyl-3-vinyldodeca-6,10-dien-1-one (2) and (2S*,3R*)-2-[(3E)-4,8-dimethylnona-3,7-dien-1-yl]-2,3-dihydro-7-hydroxy-2,3-dimethylfuro[3,2-c]coumarin (4) demonstrated the best antimicrobial activity. Compounds 2 and 4 both strongly inhibited the growth of M. luteus (MIC=11.2 and 5.2 μM, resp.) and Staphylococcus epidermidis (MIC=22.5 and 10.5 μM, resp.) and compound 2 additionally also the growth of Bacillus subtilis (MIC=11.2 μM). The cytotoxic activity of the isolates was tested against three human cancer cell lines, viz., cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562), and breast cancer (MCF-7) cells. The CHCl3 extract exhibited strong cytotoxic activity against all cell lines (IC50 <11.0 μg/ml). All compounds strongly inhibited the growth of the K562 and HeLa cell lines. Compound 4 exhibited also a strong activity against the MCF-7 cell line, comparable to that of cisplatin (IC50 =22.32±1.32 vs. 18.67±0.75μM).
对从巴尔干地区特有植物费鲁拉草（Ferula heuffelii Griseb. ex Heuff.）地下部分获得的分离物（氯仿和甲醇提取物以及选定的代谢产物）的抗菌和细胞毒性活性进行了评估。氯仿和甲醇提取物表现出中等抗菌活性，对革兰氏阳性菌的作用比对革兰氏阴性菌更明显，尤其对金黄色葡萄球菌（两种提取物的MIC均为12.5μg/ml）和藤黄微球菌（MIC分别为50和12.5μg/ml）。在所测试的代谢产物中，(6E)-1-(2,4-二羟基苯基)-3,7,11-三甲基-3-乙烯基十二碳-6,10-二烯-1-酮（2）和(2S*,3R*)-2-[(3E)-4,8-二甲基壬-3,7-二烯-1-基]-2,3-二氢-7-羟基-2,3-二甲基呋喃并[3,2-c]香豆素（4）表现出最佳抗菌活性。化合物2和4均强烈抑制藤黄微球菌（MIC分别为11.2和5.2μM）和表皮葡萄球菌（MIC分别为22.5和10.5μM）的生长，化合物2还额外抑制枯草芽孢杆菌的生长（MIC为11.2μM）。对分离物的细胞毒性活性针对三种人类癌细胞系进行了测试，即宫颈腺癌（HeLa）、慢性粒细胞白血病（K562）和乳腺癌（MCF-7）细胞。氯仿提取物对所有细胞系均表现出强细胞毒性活性（IC50<11.0μg/ml）。所有化合物均强烈抑制K562和HeLa细胞系的生长。化合物4对MCF-7细胞系也表现出强活性，与顺铂相当（IC50 =22.32±1.32对18.67±0.75μM）。
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