Tareq Fakir Shahidullah, Lee Min Ah, Lee Hyi-Seung, Lee Yeon-Ju, Lee Jong Seok, Hasan Choudhury M, Islam Md Tofazzal, Shin Hee Jae
Department of Marine Biotechnology, Korea University of Science and Technology , Daejeon 350-360, Republic of Korea.
J Agric Food Chem. 2014 Jun 18;62(24):5565-72. doi: 10.1021/jf502436r. Epub 2014 Jun 9.
Antifungal resistance and toxicity problems of conventional fungicides highlighted the requirement of search for new safe antifungal agents. To comply with the requirement, we discovered four new non-cytotoxic lipopeptides, gageopeptides A-D, 1-4, from a marine-derived bacterium Bacillus subtilis. The structures and stereochemistry of gageopeptides were determined by NMR data analysis and chemical means. Gageopeptides exhibited significant antifungal activities against pathogenic fungi Rhizoctonia solani, Botrytis cinerea, and Colletotrichum acutatum with minimum inhibitory concentration (MIC) values of 0.02-0.06 μM. In addition, these lipopeptides showed significant motility inhibition and lytic activities against zoospores of the late blight pathogen Phytophthora capsici. These compounds also showed potent antimicrobial activity against Gram positive and Gram negative bacteria with MIC values of 0.04-0.08 μM. However, gageopeptides A-D did not exhibit any cytotoxicity (GI50 > 25 μM) against cancer cell lines in sulforhodamine B (SRB), 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and WST-1 ((4-[3-4-iodophenyl]-2-(4-nitrophenyl)-2H-5-tetrazolio)-1,3-benzene disulfonate)) assays, demonstrating that these compounds could be promising candidates for the development of non-cytotoxic antifungal agents.
传统杀菌剂的抗真菌耐药性和毒性问题凸显了寻找新型安全抗真菌药物的必要性。为满足这一需求，我们从海洋来源的枯草芽孢杆菌中发现了四种新的无细胞毒性脂肽，即gageopeptides A-D（1-4）。通过核磁共振数据分析和化学方法确定了gageopeptides的结构和立体化学。gageopeptides对致病真菌立枯丝核菌、灰葡萄孢菌和尖孢炭疽菌表现出显著的抗真菌活性，最低抑菌浓度（MIC）值为0.02-0.06μM。此外，这些脂肽对晚疫病病原菌辣椒疫霉的游动孢子表现出显著的运动抑制和裂解活性。这些化合物对革兰氏阳性和革兰氏阴性细菌也表现出强效抗菌活性，MIC值为0.04-0.08μM。然而，在磺酰罗丹明B（SRB）、3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四氮唑（MTT）和WST-1（(4-[3-4-碘苯基]-2-(4-硝基苯基)-2H-5-四氮唑基)-1,3-苯二磺酸盐））试验中，gageopeptides A-D对癌细胞系未表现出任何细胞毒性（GI50>25μM），这表明这些化合物有望成为开发无细胞毒性抗真菌药物的候选物。
