Chaniad Prapaporn, Wattanapiromsakul Chatchai, Pianwanit Somsak, Tewtrakul Supinya
a Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences , Prince of Songkla University , Songkhla , Thailand ;
b Excellent Research Laboratory, Phytomedicine and Pharmaceutical Biotechnology Excellent Center, Faculty of Pharmaceutical Sciences , Prince of Songkla University , Songkhla , Thailand ;
Pharm Biol. 2016;54(6):1077-85. doi: 10.3109/13880209.2015.1103272. Epub 2016 Feb 10.
Dioscorea bulbifera L. (Dioscoreaceae) has been used in a traditional Thai longevity medicine preparation. Isolation of inhibitors from natural products is a potential source for continuous development of new HIV-1 integrase (IN) inhibitors.
The objective of this study is to isolate the compounds and evaluate their anti-HIV-1 IN activity, as well as to predict the potential interactions of the compounds with an IN.
The ethyl acetate and water fractions (1-100 μg/mL) of Dioscorea bulbifera bulbils were isolated and tested for their anti-HIV-1 IN activity using the multiplate integration assay (MIA). The interactions of the active compounds with IN were investigated using a molecular docking method.
The ethyl acetate and water fractions of Dioscorea bulbifera bulbils afforded seven compounds. Among these, allantoin (1), 2,4,3',5'-tetrahydroxybibenzyl (2), and 5,7,4'-trihydroxy-2-styrylchromone (5) were isolated for the first time from this plant. Myricetin (4) exhibited the most potent activity with an IC50 value of 3.15 μM, followed by 2,4,6,7-tetrahydroxy-9,10-dihydrophenanthrene (3, IC50 value= 14.20 μM), quercetin-3-O-β-D-glucopyranoside (6, IC50 value = 19.39 μM) and quercetin-3-O-β-D-galactopyranoside (7, IC50 value = 21.80 μM). Potential interactions of the active compounds (3, 4, 6, and 7) with the IN active site were additionally investigated. Compound 4 showed the best binding affinity to IN and formed strong interactions with various amino acid residues. These compounds interacted with Asp64, Thr66, His67, Glu92, Asp116, Gln148, Glu152, Asn155, and Lys159, which are involved in both the 3'-processing and strand transfer reactions of IN. In particular, galloyl, catechol, and sugar moieties were successful inhibitors for HIV-1 IN.
薯蓣科植物零余子薯蓣已被用于传统泰国长寿药物制剂中。从天然产物中分离抑制剂是持续开发新型HIV-1整合酶（IN）抑制剂的潜在来源。
本研究的目的是分离化合物并评估其抗HIV-1 IN活性，以及预测这些化合物与IN的潜在相互作用。
分离零余子薯蓣珠芽的乙酸乙酯和水相部分（1-100μg/mL），并使用多板整合试验（MIA）测试其抗HIV-1 IN活性。使用分子对接方法研究活性化合物与IN的相互作用。
零余子薯蓣珠芽的乙酸乙酯和水相部分得到了七种化合物。其中，尿囊素（1）、2,4,3',5'-四羟基联苄（2）和5,7,4'-三羟基-2-苯乙烯基色酮（5）首次从该植物中分离得到。杨梅素（4）表现出最强的活性，IC50值为3.15μM，其次是2,4,6,7-四羟基-9,10-二氢菲（3，IC50值=14.20μM）、槲皮素-3-O-β-D-吡喃葡萄糖苷（6，IC50值=19.39μM）和槲皮素-3-O-β-D-吡喃半乳糖苷（7，IC50值=21.80μM）。还研究了活性化合物（3、4、6和7）与IN活性位点的潜在相互作用。化合物4对IN表现出最佳的结合亲和力，并与各种氨基酸残基形成强相互作用。这些化合物与Asp64、Thr66、His67、Glu92、Asp116、Gln148、Glu152、Asn155和Lys159相互作用，这些氨基酸参与IN的3'-加工和链转移反应。特别是，没食子酰基、儿茶酚和糖部分是HIV-1 IN的成功抑制剂。
